CHAPTER VI. Conductivity

CONDUCTIVITY

Contents: Only processes of excitation are conducted, not processes of depression. Conduction of excitation in its two extreme instances. Conduction in undifferentiated pseudopod protoplasm of rhizopoda. Conduction of excitation with decrement of intensity and rapidity. Conduction of excitation in the nerve. Rapidity of conduction of excitation without decrement. Relation between irritability and conductivity. Conduction of excitation with decrement of the nerve after artificial depression of irritability by narcosis. Theory of the decrementless conduction of the normal nerve. Proof of the validity of the “all or none law” in the medullated nerve. Theory of the process of the conductivity of excitation. Theory of core model (Kernleiter). Electrochemical theory of conduction based on the properties of semi-permeable surfaces.

When the response to a stimulus is studied in a living system, whether it be a single cell, a tissue, or a complex organism, the indicator used, either that of movement, current of action, production of certain substances, the development of light, of heat or the alteration of form, is the result of two distinct processes. The first of these is primary excitation, brought about by the stimulus at a local point, and the second is an extension of the excitation to the surrounding tissue. We are not in a position to experimentally bring about a response to stimulation, in which the primary excitation occurs and not the secondary process, that of conductivity. All living substance contains this property, although to a very different degree, as all living substance possesses irritability, and this presents the condition not only for the taking place of the process of excitation but also that of its conduction.

If I here speak only specifically of the conduction of excitation instead of the conductivity of response to stimulation this is not only primarily for the reason that we intend especially to analyze the conductivity of excitation on this occasion, but also because no other effects of stimulation except those of excitation can be conducted from the part affected by the stimulus to the surroundings.

Although considered on theoretical grounds it appears more or less improbable that depression is extended from the place of its origin, it is very easy to convince one’s self experimentally of the fact that depression following a stimulus is invariably localized to that portion directly affected by the stimulus. The nerve furnishes a very favorable object for this purpose. If a nerve muscle preparation of the frog is made and introduced in the glass chamber previously described containing platinum electrodes, and another pair is applied to the nerve between the chamber and the muscle, it is possible to subject the stretch of nerve in the chamber to various agents, producing a paralyzing effect. In this way it may be exposed to an atmosphere of pure nitrogen for example, or to narcosis as by ether, chloroform, carbon dioxide and other gases, to an increase in temperature or to other agents, without these in any way affecting the irritability of the nerve stretch situated over the electrode between the chamber and the muscle. The contractions of the muscle, which are produced by stimulation of the periphery region of the nerve with stimuli of a definite strength, remain unaltered, even when the asphyxiated stretch of nerve in the chamber is already completely degenerated. The central depression of a ganglion cell of a motory neuron is likewise wholly without influence on the degree of excitability of its nerve fiber, as I was able to demonstrate in the reflex inhibition of the motor neurons of the spinal cord of the dog. (Figure 14.) That which is conducted by the nerves is solely the process of excitation.

Max Verworn: “Zur Physiologie der nervösen Hemmungserscheinungen.” Arch. f. Anat. u. Physiol. physiol. Abt. Suppl. 1900.

It is our task to analyze in detail the conditions involved in the conduction of excitation in order to obtain a deeper insight into the physics of this process. A comparative survey of a series of various types of living substance shows us that they differ in respect to the conduction of excitation in the following points: In regard to the rapidity with which the excitation is conducted, the extent of the area over which it spreads, and the intensity with which it extends. These conditions may be best illustrated by citing two extreme examples. The one is formed by the rhizopods, the other by the nerve fibers. Between these two extremes we have manifold gradations in the conditions of conductivity. Not all cell forms are suitable objects for the study of conductivity. There are forms of rhizopods which are as favorable to investigation as the nerve; this is due to the fact that, although they are often of microscopic dimensions, they possess elongated fingerlike or threadlike pseudopods.

Contractions of the musculus extensor digitorum communis longus of the dog, brought about by rhythmic stimulation of the nervus peroneus. The muscle is in the condition of tonic excitation which proceeds from the center. The arrows indicate the point where reflex inhibition of the central tonus is produced. The height of the single contraction undergoes no diminution. ]

Indeed, a rhizopod cell, with its straight, elongated pseudopods, is preëminently fitted as an object of comparison with a neuron. Although the difference in respect to the individual points is so far-reaching, still, based on their outward morphological similarity various physiological parallels in both are forced on our observation. A comparison of the rhizopod cell with the neuron can consequently guard us from many erroneous generalizations which we might be inclined to deduce from a one-sided investigation of the nerve. This is especially the case in regard to the conductivity of excitation, which was formerly studied almost exclusively on the nerve and only occasionally on the muscle, which offers similar conditions. The nerve, in which the function of the conductivity of excitation is particularly highly developed, was considered at the same time as the type in which this process could be most readily analyzed, and from which it was believed general information of the process of the conductivity of excitation could first be gained. This view has led to serious errors, as the nerve, resulting from the high development of its conductive capability, shows quite one-sided specialized conditions, which can by no means be transferred to other forms of living substance.

A very suitable object among rhizopods for the study of conductivity, and which is everywhere easily procured, is Difflugia. This species living in small pools has a delicate urn-shaped, pear-shaped or flask-shaped capsule built up of sand grains, diatomes or material produced by the organism itself. From the opening the protoplasm extends often to a considerable length its finger-shaped hyaline pseudopods. When Difflugia is placed in a flat dish in water and observed under the microscope, it is frequently seen to extend from the opening long pseudopods in exactly opposite directions, which reach for a considerable distance on the bottom. These offer particularly favorable conditions for the study of the conduction of excitation. When this animal is placed under a microscope, the pseudopods are very readily stimulated at any position to a desired extent by means of a sharp needle, to which fat has been previously applied and subsequently the excess removed. The extension of the response from one point toward the other can then be followed with great ease. The pseudopod of the rhizopod has the great advantage over the nerve that its excitation can be directly observed. The excitation following weaker stimulation is manifested by a wrinkling of the previously completely smooth surface; stronger stimulation produces differentiation of the hyaline protoplasm to a strongly refractive strand in the axis and a turbid myelinlike mass at the periphery, the pseudopod at the same time retracting toward the central cell body. In spite of all these occurrences being of microscopic dimensions, still with some practice it is quite possible to experiment on them under the microscope. In this way I found it comparatively simple to study the fundamental principles of conductivity.

Max Verworn: “Psycho-physiologische Protistenstudien. Experimentelle Untersuchungen.” Jena 1889.

Difflugia urceolata. A--Weak local stimulation at the end of a long extended pseudopod. B--Stronger local stimulation applied to the end of a long pseudopod.]

Difflugia urceolata. A--In non-stimulated condition. B--The same individual locally stimulated in the middle of a long extended pseudopod. The excitation spreads in both directions, centripetal as well as centrifugal. ]

All these factors, the intensity with which the excitation extends from the point of stimulation, the rapidity of the extension, and finally the area over which conduction takes place, are manifestations of the intensity of stimulus, and as such alter with these in corresponding manner. If the end of a pseudopod is barely touched and thereby weakly stimulated, the response is restricted to a slight wrinkling of the surface, which slowly extends to the immediate neighborhood, whilst the more distant parts of the pseudopod are not affected at all by the excitation. (Figure 15, A.) On a stronger stimulation of the pseudopod by slight pressure, the response is likewise stronger, and the characteristic differentiation of the protoplasm, consisting in the strongly refractive strand in the axis and the turbid myelinlike outer mass, appears at the point of stimulation. From here a peculiar alteration spreads gradually further over the pseudopod, in that first upon its smooth surface a few myelinlike droplets are seen, which become larger and with the development of the strand in the axis, dissolve into a wrinkled mass on the surface. The further this process extends from the point of stimulation, the weaker it becomes and the more slowly it proceeds, until at last there is complete disappearance. (Figure 15, B.) The pseudopod has at the same time retracted to a considerable degree. If a still stronger stimulus is applied by firm pressure at the end of the pseudopod the process takes place with much greater violence. The differentiation of the protoplasm spreads centripetally from the point of stimulation over the whole pseudopod with great rapidity, and produces a quick retraction in the same, then involves the oppositely directed pseudopod, in which it then extends more and more slowly, until, proceeding in a centrifugal direction, it is at last gradually completely obliterated. When strong stimulation is applied, the process occurs with such rapidity that the contraction of the pseudopod is almost twitchlike. As the rapidity of the conduction alters within a wide limit according to the strength of the stimulus and the distance from the point of stimulation, it is self-evident that no constant figure can be stated. To give a general idea of the rapidity, they might be estimated according to observations I have made with second watch and ocular-micrometer as from within a slight fraction to that of a millimeter in the second. When a very long extended pseudopod is locally stimulated in the middle, the response spreads from the point affected in both directions diminishing in intensity and rapidity. The excitation extends equally in all directions. (Figure 16.) These facts show very clearly that in Difflugia the excitation following a localized stimulus is dependent on the intensity of the stimulus, and that according to the degree of this, the wave progresses in either stronger, more rapid and extended, or weaker, slower and more limited manner. With the greater distance from the point of stimulation the excitation undergoes an increasing decrement of its intensity and rapidity of conduction. Different species of Difflugia which I have investigated, Difflugia lobostoma, urceolata, pyriformis, have shown a complete conformity in this respect. A great number of other fresh water and marine rhizopods, the pseudopods of which I have used for analogous experiments, although differing in the manner of reaction in regard to the extent and rapidity of the course of excitation, manifest exactly the same fundamental principles. A very favorable form is, for instance, the much smaller Cyphoderia margaritacea, which is distinguished by a somewhat higher degree of excitability and rapidity of reaction. The long straightly extended pseudopods are thinner and more threadlike than those of Difflugia and show upon stimulation as a result of their local excitation a simple contraction into clumps of the stimulated protoplasm without the characteristic differentiation of that of Difflugia. (Figure 17.) In the case of the marine rhizopods, Orbitolites (Figure 19), Amphistegina, etc., which I investigated at the Red Sea, the conduction of excitation takes place also as in Difflugia with a decrement of intensity and rapidity becoming larger with the distance from the point of stimulation until the wave of excitation is obliterated.

Max Verworn: “Die Bewegung der lebendigen Substanz. Eine vergleichend physiologische Untersuchung der Contractionserscheinungen.” Jena 1892.

Cyphoderia margaritacea. Result of localized mechanical stimulation at the end of a long extended pseudopod. A, B, C--three successive stages.]

Cyphoderia margaritacea. Result of localized mechanical stimulation in the middle of a long extended pseudopod.]

A pseudopod of Orbitolites complanatus (cf. Fig. 7). a--In normal condition. b--Severed by a cross section near the end. b-f--Five successive stages of the effect. b-d--The pseudopod retracts by centripetal flowing of the protoplasm contracted in the shape of microscopic balls and spindles. e and f--The pseudopod begins to extend again. The centripetal flowing balls and spindles begin to disappear. ]

A sharp contrast to this type is formed by the other extreme as represented by that of the medullated nerve. As an indicator of the course of excitation we will take the action current in an isolated nerve of the frog. If this is stimulated at one end, we can test the intensity of the conducted excitation by leading off the action current from two points at varying distances from the one influenced by the stimulus. Since the classical discovery of Du Bois-Reymond of the action current of the nerve, we know that in the fresh medullated nerve, if observed under favorable experimental conditions, no decrement of intensity of excitation during its course from the point of stimulation along the length of the nerve can be demonstrated. If unpolarizable electrodes are applied to a nerve in such a position that they are equidistant from the cross section and are connected with apparatus for testing the current, it will be found that there exists an “unwirksame Ableitung” in the sense of Du Bois-Reymond, that is, in which there is no demarcation current. When a tetanizing current is applied to one end of the nerve, no difference of potential between the two nonpolarizable electrodes is observed, which indeed would be the case if excitation with its current of action would have a decrement on its way from one to the other point of leading off the current. This fact, which has been repeatedly confirmed, shows us that the medullated nerve, under normal conditions, conducts excitation without a perceptible decrement of the intensity.

Du Bois-Reymond: “Untersuchungen über tierische Electricität.” II Band. 1849.

This specific property of a medullated nerve is in conformity with the conditions in connection with the rapidity of conductivity. Since Helmholtz has devised the method for measuring the rapidity of conduction in the nerve, this investigator himself and numerous others have studied the rate in different nerves. Helmholtz found the rate for motor nerves of the frog to be 27 meters per second, for the sensory nerves of man 60 meters, and the motor nerves of man 34 meters. Other investigators have obtained quite different results; Hirsch, for the sensory nerves of man, 34 meters; Schelske, for the same, 25–33 meters; De Jaager, 26 meters; v. Wittich, 34–44 meters, and Kohlrausch, 56–225 meters; v. Wittich for the motor nerves of man, 30 meters; Piper finally in the most recent investigations about 120 meters in the second.

H. Helmholtz: “Messungen über den zeitlichen Verlauf der Zuckung animalischer Muskeln und die Fortpflanzungsgeschwindigkeit der Reizung des Nerven.” Müller’s Archiv. 1850.

The same: “Messungen über die Fortpflanzungsgeschwindigkeit der Reizung in den Nerven.” Zweite Reihe, Müller’s Arch. 1852.

Compare: Hermann: “Handbuch der Physiologie.” II, 1 Leipzig 1879.

Piper: “Ueber die Leitungsgeschwindigkeit in dem markhaltigen menschlichen Nerven.”

The same: “Weitere Mitteilungen über die Geschwindigkeit der Erregungsleitung im markhaltigen menschlichen Nerven.” Pflügers Arch. Bd. 127, 1909.

These differences may be explained in a large measure by the variety of the methods used, in part also by the difference in the structures. The methods employed for the study of the velocity have also been used to solve the question, whether the velocity of the excitation wave in its course over the nerve meets with a decrement as it moves further and further away from the point of stimulation. Here the endeavor was made to study the difference in time of the latent period, which is observed by the indicator, when the nerve is stimulated at two points at different distances from the muscle, used as an indicator, or from the wires leading the current to the indicator. The more recent investigators, as René Du Bois-Reymond, Engelmann, G. Weiss, have arrived at the same conclusion, that the rate of conductivity in the medullated nerve under normal conditions is the same at all distances from the point of stimulation. (Figure 20.)

R. Du Bois-Reymond: “Ueber die Geschwindigkeit des Nervenprincips.” Arch. f. Anat. u. Physiol. physiol. Abt. Suppl. 1900.

Engelmann: “Graphische Untersuchungen über die Fortpflanzungsgeschwindigkeit der Nervenerregung.” Arch. f. Anat. u. Physiol. physiol. Abt. 1901.

G. Weiss: “La conductibilité et l’excitabilité des nerfs.” In Journ. de Physiol. et de Pathol. générale 1903.

The medullated nerve shows, therefore, under normal conditions neither a decrement of its conductivity, nor of its irritability, as the distance of the wave of excitation increases from that of the position of stimulation; this means, in other words, that excitation is conducted with the same intensity with which it is started, and with a constant rate throughout the entire course of the nerve.

Curves of muscle contraction obtained by stimulation of 3 and 4 points situated at equal distances from each other on the sciatic nerve of the frog. The increase of length of the nerve stretch corresponds with an equal increase of the latent period of contraction. From this follows, that the rapidity of the wave of excitation is the same at all points of the entire length of the nerve. (After Engelmann.) ]

There is, nevertheless, a third point of considerable difference between the types of conduction of excitation in the rhizopods and in the nerve. Whereas in the rhizopods the rapidity of conduction is dependent upon the intensity of the stimulus, it has been long known as the result of investigation by Rosenthal, Brücke and Lautenbach and at a more recent date by Gotch and Piper, that in the nerve of the frog, as well as in man, the velocity is not dependent upon the intensity of stimulation. (Figure 21.) Contrary results have been obtained by a few early observers wherein the latent period was shorter when the stimulation was strong. Nicolai explains this shortening of the latent period, resulting from the application of strong electrical stimuli, to a spreading out of the “Stromschleifen” from the point of application and consequently there is a shortening of the stretch of nerve between the point of stimulation and the indicator.

Gotch: “The submaximal electric response of nerve to a single stimulus.” Journal of Physiology, Vol. XXVIII, 1902.

Piper: Ueber die Leitungsgeschwindigkeit in den markhaltigen menschlichen Nerven. Pflügers Arch. Bd. 124, 1908, und Bd. 127, 1909.

Nicolai: “Ueber Ungleichförmigkeiten in der Fortpflanzungsgeschwindigkeit des Nervenprincips, nach Untersuchungen am marklosen Riechnerven des Hechts.” Arch. f. Physiologie 1905.

Course of the action current of the nerve. The thin line indicates the action current produced by a weak, the thick line the action current produced by a strong stimulus. The duration of the action current is the same in both cases. (After Gotch.) ]

This conspicuous difference in the conduction of the two extreme types of living substance, which we have already observed, arouses the question as to what properties of living substance bring about these differences. In order to answer this question, it is necessary, first of all, to make some general statements concerning the processes of conductivity.

As already emphasized, all living substance possesses the capability of conducting excitations to a definite degree. We may, therefore, assume that the same fundamental property of conductivity exists in all substances. A fact to be considered in the conduction of excitation, is that the primary breaking down of the complex molecules at the position of stimulation act in turn as exciting stimuli upon the neighboring portion of the living substance, which in turn undergoes a similar decomposition. And so this process continues. This fact is evident from the observations on the process of excitation. But the nature of the stimulus which produces the breaking down of the complex molecules upon the surrounding molecules is a problem which can only be studied later. Here only one point will be mentioned in advance concerning the intensity of the stimulus. It is apparent from the experiments on the rhizopods, that the greater the intensity of the stimulus the more extensive must be the breaking down of the living substance. A stronger primary stimulation must also secondarily produce a stronger stimulus in the neighborhood. In other words: the conduction of excitation is a function of irritability. The greater the irritability, that is, the greater the number of molecules broken down in a unit of time and space by a stimulus of a certain intensity, the greater also is the conductivity of the living system, that is, the stronger, the more rapidly and the further excitation is extended. Conductivity of excitation is, therefore, unthinkable without irritability. Both are inseparably connected. The conclusion forced upon us by this chain of reasoning admits of no argument. Nevertheless the endeavor has been made, because of certain evidence at hand, to show that the property of conductivity could exist without irritability. A number of authors, such as Schiff, Erb, Grünhagen, Effron, Hirschberg and G. Weiss, have observed the fact that in spite of a more or less strong decrease of excitability of a stretch of nerve, stimuli applied above this stretch can still produce a conduction of excitation through the affected part. They have concluded from this that it is possible to separate the conductivity from irritability. Erb and G. Weiss have even gone so far as to directly express the opinion that capability of conduction and irritability involve two different histological elements. In contrast to this, other investigators, such as Hermann, Szpilmann and Luchsinger, Gad, Piotrowski and Wedenski, have more or less decidedly taken the stand that an actual separation of irritability and of conductivity does not exist. The apparently contradictory evidence as well as the conflicting theoretical views have been cleared up by Werigo, Dendrinos, Noll and Fröhlich. These investigators have shown that the length of the narcotized stretch of the nerve plays an important rôle in the obliteration of conductivity. It has been found by the application of a stimulus above the narcotized stretch of nerve, that the longer this stretch is, the less is the reduction of irritability which obliterates the excitation wave reaching this area. Further: The shorter the stretch, the greater must be the reduction in irritability before this result is brought about. (Figure 22.) In other words, the conductivity in the narcotized nerve is dependent upon the length and the irritability of the narcotized stretch. From this observation the important fact is evolved, that the wave of excitation meets with a decrement of its intensity in the narcotized area. This decrement becomes larger as the wave progresses through the involved stretch. Further it is progressively increased as the amount of the irritability is reduced. Finally, when the stretch is long enough, the wave of excitation is obliterated. This important fact has been further established by the experiments of Boruttau and Fröhlich, in which they studied the intensity of the current of action, produced by a wave of excitation, from two points in the narcotized stretch. The wave of negative variation, brought about by the excitation, gradually decreases in the narcotized stretch as the electrode is further removed from the point of entrance. Beside a decrement of intensity, as the investigations of Fröhlich prove, the wave of excitation shows a decrement of the velocity in the narcotized stretch. And it is probable that the wave of excitation extends with progressive reduction in the velocity, corresponding to the decrement of intensity. The work of Koike under the direction of Garten, in which the conclusion arrived at is that the reduction in the velocity is the same throughout the narcotized area, should not be accepted as conclusive in spite of the delicate method employed. These investigations are extremely difficult, being in the field of the most delicate of present-day methods. The decrement, which the wave of excitation meets with in its progress in the narcotized stretch, makes the conflicting testimony concerning the apparent separation of irritability and conductivity intelligible. It depends entirely upon the length of the narcotized area, and the amount of reduction in irritability on the one hand, and the strength of the stimulus used for testing the irritability on the other, whether the conductivity will disappear before the irritability or vice versa. If I test the irritability in the narcotized stretch with a weak stimulus, just slightly above the threshold, then by slight reduction in the irritability complete absence of response occurs, when the same stimulus is applied. This occurs at a time when excitation reaches the narcotized area from above and meets with a decrement so slight that it can pass through the whole narcotized stretch, that is, when the narcotized stretch is short enough. If I test the irritability of the narcotized area with a strong stimulus, far above that of the threshold, irritability will be found to be present at a time when the conductivity for the excitation, coming from above, is already obliterated. This is due to the fact that the decrement in the narcotized area is already great enough to bring about the complete disappearance of the wave of excitation coming from above. This, of course, only occurs provided the length of the narcotized stretch is great enough. The separation of conductivity and irritability is, therefore, only an apparent one. In reality, the facts obtained from experimentation indicate that with the reduction of irritability the decrement of the wave of excitation increases, whilst the shorter the stretch, the smaller is the decrement. This shows that conductivity is a manifestation of irritability.

Schiff: “Über die Verschiedenheit der Aufnahmsfähigkeit und Leitungsfähigkeit in dem peripherischen Nervensystem.” Henle u. Pflügers Zeitschr. 1866.

Erb: “Zur Pathologie und pathologischen Anatomie peripherischer Paralysen.” Deutsches Arch. f. Klin. Med. 1869.

Grünhagen: “Versuche über intermittierende Nervenreizung.” Pflügers Archiv. Bd. 6, 1872.--Funke-Grünhagen. Lehrbuch der Physiologie Bd. I, 1876.

Effron: “Beiträge zur allgemeinen Nervenphysiologie.” Pflügers Arch. Bd. 36, 1885.

Hirschberg: “In welcher Beziehung stehen Leitung und Erregung der Nervenfaser zu einander?” Pflügers Arch. Bd. 39, 1886.

G. Weiss: “La conductibilité et l’excitabilité des nerfs.” Journ. de physiol. et de pathol. générale. T. V. 1903.--“Influence des variations de temperature et des actions méchaniques sur l’excitabilité et la conductibilité des nerfs.” Ibidem.

Hermann: “Handbuch der Physiologie.” Bd. II, I Leipzig 1879.

Szpilmann und Luchsinger: “Zur Beziehung von Leitungs- und Erregungsvermögen der Nervenfaser.” Pflügers Arch. Bd. 24, 1881.

Gad: “Ueber Trennung von Reizbarkeit und Leitungsfähigkeit des Nerven.” (Nach Versuchen des Herrn Sawyers) Arch. f. Anat. u. Physiol. physiol. Abt. 1888.

Derselbe: “Ueber Leitungsfähigkeit und Reizbarkeit des Nerven in ihren Beziehungen zur Längs- und Querschnitts erregbarkeit.” Nach Versuchen des Herrn Piotrowski Arch. f. Anat. und Physiol. physiol. Abt. 1889.

Piotrowski: “Ueber Trennung von Reizbarkeit und Leitungsfähigkeit des Nerven.” Arch. f. Anat. u. Physiol. physiol. Abt. 1893.

Wedenski: “Die fundamentalen Eigenschaften des Nerven unter Einwirkung einiger Gifte.” Pflügers Arch. Bd. 82, 1900.

The same: “Excitation, inhibition et narcose.” Compt. rendus du v. Congres internat. de Physiologie à Turin 1901.

Werigo: “Zur Frage über die Beziehungen zwischen Erregbarkeit und Leitungsfähigkeit des Nerven.” (Nach Versuchen von stud. Rajmist.) Pflügers Arch. Bd. 76, 1899.

Dendrinos: “Ueber das Leitungsvermögen des motorischen Froschnerven.”

Noll: “Ueber Erregbarkeit und Leitungsvermögen des motorischen Nerven unter dem Einfluss von Giften und Kälte.” Zeitsch. f. Allgem. Physiol. Bd. III, 1907.

Fr. W. Fröhlich: “Erregbarkeit und Leitfähigkeit des Nerven.” Zeitschr. f. allgem. Physiol. Bd. III, 1904.

Boruttau und Fröhlich: “Erregbarkeit und Leitfähigkeit des Nerven.” Zeitschrift f. allgem. Physiologie Bd. IV, 1904. The same: “Electropathologische Untersuchungen ueber die Veränderungen der Erregungswelle durch Schädigung des Nerven.” Pflügers Arch. Bd. 105, 1904.

Fröhlich: “Die Verringerung der Fortpflanzungsgeschwindigkeit der Nervenerregung durch Narkose and Erstickung des Nerven.” Zeitschrift allgem. Physiologie Bd. III, 1904.

Izuo Koike: “Ueber die Fortleitung des Erregungsvorgangs in einer narkotisierten Nervenstrecke.” Zeitsch. f. Biologie Bd. 5, 1910.

Scheme of the decrement of the excitation wave in the narcotized stretch of a nerve. A--The narcotized stretch (indicated by the cross section of the chamber) is 30 mm. long. The ordinates of the dotted lines indicate the amount of the decrement. If the decrement is slight (upper dotted line), the excitation wave passes the narcotized stretch and increases again on entering the normal stretch. If the decrement is great (lower dotted line), the excitation wave is obliterated towards the end of the narcotized stretch and the muscle remains at rest. B--The narcotized stretch is 15 mm. long. The decrement is slight. The excitation wave can therefore pass into the normal stretch and here increase again. C--The narcotized stretch is 15 mm. long. The decrement is great. The excitation wave is obliterated, therefore, in the narcotized stretch, and the muscle remains at rest. ]

The facts just mentioned have, however, a much deeper meaning. They show us that it is possible by means of narcosis to convert an extreme type of a living system, with decrementless conductivity, into another extreme type of living substance, in which excitation in its progress meets with a strong decrement, like that seen in the rhizopods. The same results may also be obtained by asphyxiation and other forms of temporary and permanent injury of the nerve. We are, therefore, in the fortunate position in the case of the medullated nerve of having a substance to study, which, depending upon conditions which are under our control, may become a type in which conductivity occurs with or without the presence of a decrement. We can likewise reduce the irritability to various degrees, producing all intermediate gradations between the two extremes. This latter is particularly valuable in that it permits us to study the conditions in one and the same substance necessary to bring about the various peculiarities of conductivity. The great differences in the conductivity of excitation are conditioned by variations in the degree of irritability. If the irritability of the nerve is at the normal level the wave of excitation progresses to the end of the nerve without manifesting a decrement of its intensity or rapidity.

If the level of irritability of the intact nerve is artificially reduced, the wave of excitation meets with a greater decrement and reduces in velocity, and in fact disappears the more quickly in the stretch of nerve, as the reduction in irritability is increased. These three factors, irritability, intensity and velocity of the progress of the wave of excitation, are inseparable. All living substances may be grouped according to their capability of conducting excitation into a long series, starting with those possessing the least irritability, as we found in the rhizopods, then those having greater irritability, as the smooth muscle and ganglion cells, then those with still greater irritability, as the striped muscle, and finally those having the greatest degree of irritability, as the medullated nerves of the warm-blooded animal. Should the processes of excitation, as we saw, result from the energy production following the disintegration of the labile molecules of the living substance, then the degree of irritability is determined by the chemical constitution of the disintegrating molecules, by the number of molecules which are broken down in a definite space and a given time, and by the nature of the disintegration itself. All of these individual components, if we observe the problem from the physical standpoint, are manifested by the quantity of energy production. The higher the irritability of a living system, the greater is the amount of energy production in a given time and space which the stimulus produces. This has particular interest from the standpoint of the extreme cases of medullated nerves of the vertebrates with their most highly developed conductivity, and which will be analyzed in somewhat greater detail. How are we to explain their decrementless conductivity? When we study the decrement of the excitation wave in the series of living substances, before alluded to, we see that this reduces with a progressive increase of irritability. Consequently the extreme irritability of the nerve is a manifestation of its decrementless conductivity. If we study the course of a process of excitation and its conduction in its molecular details, the fact of the decrementless conduction indicates that in excitation, produced by a stimulus, the same number of specific molecules capable of disintegration are broken down in the same manner at every following cross section, as at the point of stimulation; or in other words: an equal amount of energy is set free at every cross section, which, in its turn, acts as stimulus to the next, etc. Such a condition presupposes, however, in an elementary fiber of the nerve, that by the conduction of the wave of excitation from cross section to cross section, all those molecules capable of disintegration are broken down. If it is assumed that the entire number of molecules capable of disintegration do not break down, but only a certain per cent. of the same, then it would not be possible to conceive of a molecular structure of the nerve in which this would take place without decrement of the wave of excitation. With the assumption of a generally homogeneous molecular structure (Figure 23, a) of the elementary fibers it would be entirely incomprehensible how, with the decrementless extension of the excitation, individual molecules capable of breaking down could escape disintegration. If, on the contrary, the molecular structure is not homogeneous it only is possible to explain a conduction, on each cross section of which an equal per cent. of irritable molecules break down, by the hypothesis that the irritable molecules are in their turn ordered in fiber-shaped series (Figure 23, b) within the elementary fiber and are thus protected to a certain degree from one another and from transverse conduction of excitation. This hypothesis would, therefore, only mean that the elementary fiber is not such in reality and would thus transfer the difficulty to the ultimate fiber unit, for which a homogeneous molecular structure would have to be presumed. In short, whatever may be the assumption on which molecular structure of elementary fibers is based, the fact of the decrementless conduction peremptorily demands, from the physical standpoint, that from cross section to cross section the entire number of irritable molecules are broken down. This conclusion is highly important, for it indicates very clearly that the “all or none law” is applicable to the nerve.

This gives us occasion to return to the discussion of the question, if living systems really exist which respond in accordance with the “all or none law.” The medullated nerve forms an object particularly suited to serve as a starting point for the treatment of this especially important problem. The question arises in this connection, if the validity of this law for the nerve can be tested by other means.

At first it would seem as if the application of the “all or none law” to the nerve were in contradiction to the well-known fact that a weak stimulation of the nerve produces a weak, a strong stimulation, a strong response. In this connection Gotch has pointed out, as the result of experimental studies of the wave of activity of the nerve, that the difference in response, following the application of stimuli of varying strengths, is understandable from the fact that threshold stimuli stimulate only a few of the fibers of the nerve trunk, whereas progressively increasing the intensity of the current involves more and more fibers. There can be no doubt that this factor explains the difference in the strength of the response. Therefore, in reality we do not find here a contradiction of the “all or none law.” On the other hand, the fact that the nerve, in contradistinction to many other forms of living substance, the ganglion cell, for example, upon a weak stimulation does not show the phenomena of summation, even when the stimuli follow each other in a rapid succession, indicates very strongly that the weakest operable stimulus produces maximal excitation, so that the response cannot be further increased. But above all, there is a series of facts, which have been gained in the Göttingen laboratory, which demonstrate apparently without doubt the validity of the “all or none law” for the medullated nerve. These observations I wish now to consider in greater detail.

Gotch: “The submaximal electrical response of nerve to a single stimulus.” Journal of Physiology, Vol. XXVIII, 1902.

If a nerve of a nerve muscle preparation is drawn through a specially devised glass chamber so that the middle portion can be narcotized or asphyxiated and the nerve so arranged that it rests upon a pair of electrodes in the chamber and upon a second pair without the chamber and centrally located, then the nerve can be narcotized or asphyxiated and thereby the alterations in the irritability as well as the conductivity can be followed. In order to obtain as distinct a picture of this alteration as possible, I tested continuously the threshold of stimulation, which just produced minimal contraction in the muscle, and Fröhlich continued these observations. As a result the following very remarkable conditions were observed. During the increase of the depth of narcosis or asphyxia the irritability sinks more and more with regularity. The conductivity remains unaltered for a long time, as the strength of the threshold stimulus is not changed until irritability has fallen to a definite point. When this is reached, conductivity disappears. (Figure 24.) The most important point in this connection, however, is, that the conductivity disappears simultaneously and practically momentarily for the excitation produced by both weak and strong stimuli. When the stimulation at the electrode placed centrally to the chamber does not bring about response for threshold stimuli, maximal stimuli at the same time also become inoperative. This is a very interesting point, the importance of which has not until now been recognized. This fact is not in harmony with the view held until now, that in the nerve fiber different strengths of stimuli bring about excitation of different intensity, and are then conducted. Let us now clearly comprehend this problem.

Fröhlich: “Erregbarkeit und Leitfähigkeit des Nerven.” Zeitschr. f. allgem. Physiologie, Bd. III, 1904.

Curves of the changes in irritability (p) and conductivity (c) of a nerve under the influence of narcosis or asphyxiation. (After Fröhlich.)]

We have already seen that the wave of excitation meets with a decrement of its intensity in the narcotized stretch, which increases in strength as the irritability diminishes. If the value of the threshold is learned by stimulating the nerve at the electrodes centrally placed to the chamber with minimal stimuli, it would necessarily follow that this weak stimulus would bring about a corresponding weak excitation of the individual fibers and the wave of excitation already in the beginning of narcosis would be obliterated, for it would meet with a decrement, the result of the reduction in the irritability. A wave of excitation of minimal strength could under these conditions no longer reach the muscle, even in the beginning of narcosis. In spite of this the excitation, even when produced with threshold stimuli, passes through for a long time, even when the irritability in the chamber is greatly reduced, as shown by testing with the electrodes within the chamber. This is not consistent with the assumption that a threshold stimulus brings about the minimal excitation, even in the individual nerve fiber. But further: with a definite decrease of irritability of the narcotized stretch the capability of conductivity disappears, and indeed simultaneously for the weakest as well as the strongest stimuli. If it is assumed that weak stimuli bring about weak excitations in the nerve fiber, it must most certainly be expected that on the cessation of the response, weak stimuli applied at the central nerve end would still, by slight increase of the intensity of stimulation, be followed anew by reaction in the muscle. This is all the more to be expected, because the irritability of the narcotized stretch, as shown by stimulation with the electrodes inside the chamber, very gradually decreases, so that within the chamber stimuli of moderate strength are still effective. Instead the capability of conduction is completely obliterated, and even the strongest stimuli, applied to the end of the nerve, produce no response in the muscle. This in turn does not agree with the assumption that the intensity of excitation varies with the strength of the stimulus in the individual nerve fiber. The facts here alluded to are, therefore, either not correct, or the intensity of excitation in the individual nerve fibers is independent of the strength of the stimulus, and the view which we have entertained up to the present in this respect is incorrect.

In order to examine these facts once more on an extensive scale, and at the same time obtain an understanding of the development of the decrement in the narcotized stretch, I have requested Dr. Lodholz to register as many accurate curves as possible in which the positions of the secondary coil of an inductorium are the ordinates indicating the threshold of stimulation at four points of a nerve stretch. Of these points three are situated at prescribed distances from each other in the narcotized or asphyxiated stretch; the fourth is centrally placed. (Figure 24.) As might be expected the result was the same as in former investigations. They show however even more strikingly the abruptness of the disappearance of conductivity simultaneously for the weakest and the strongest stimuli. The curve produced by the centrally placed electrode remains at the same height for a considerable period, then suddenly abruptly declines. Those of the electrodes within the chamber likewise sink, at first slowly, then with increasing rapidity in successive order corresponding to the distance which they are situated from the point of exit of the nerve, so that the curve of the most distant electrode reaches the abscissa first, that of the electrode nearest the muscle in the chamber, last. The experiments demonstrate with complete clearness that in contrast to all those points within the affected stretch, where the conductivity, though already obliterated for weaker stimuli, still exists for stronger, that with stimulation of a point towards the center above the affected stretch, conduction ceases simultaneously for all different strengths of stimuli. This last state at the points within the affected stretch might be ascribed to the diminution of the excitability of this stretch, and the idea entertained that the weak stimuli no longer produce excitation capable of further conduction.

This assumption is contradicted, however, by the fact that subsequently to the disappearance of the response at a point situated at the greatest distance from the place of exit, an effect of stimulation can be obtained at the nearest point to the exit with the same or even less strength of the current. As the irritability in the affected stretch is reduced at all points in equal measure, the fact of a weaker stimulus becoming inoperative whilst a stronger remains effective can only be attributed to the circumstance that the wave of excitation set free at some point of the influenced stretch by a weaker stimulus is sooner obliterated on its way to the muscle than that produced at the same point by a stronger stimulus. These experiments, in which the manifestations of the nerves in response to stimuli applied centrally above the chamber in the normal stretch are compared to those in response to a stimulus acting on the affected stretch, clearly demonstrate the totally different effect in both cases. In stimulation of the centrally situated normal stretch, the wave of excitation, which enters from here into the influenced stretch, is obliterated at the same point simultaneously for the weakest as well as for the strongest stimulus; stimulation of the affected stretch, the wave of excitation which is set free at one point by a weak stimulus, is obliterated sooner and after passing through a shorter stretch than that which is produced by a stronger stimulus. It is self-evident that in the first instance, in which the stimulus acts on the centrally situated normal stretch, the wave of excitation, thereby set free, must in passing through the affected stretch undergo a decrement of its intensity. If, therefore, the wave of excitation, coming from above, is obliterated exactly at the same point, whether brought about by weak or strong stimuli, the inevitable conclusion must be drawn that, whether either a weak or a strong stimulus is operative, the wave of excitation must have entered into the influenced stretch from the normal stretch with exactly the same intensity. In other words: the weakest as well as the strongest stimuli produce excitations of equal intensity in the normal nerve, that is, the “all or none law” is valid for the nerve.

This information can no longer be doubted in the presence of such evidence as was presented above. This indeed is a fact of far-reaching importance in the understanding of the functional activity of our nervous system, for it is evident that the difference of intensity in the conduction of excitation is not, as has been assumed until now, the result of the conduction of varying strengths of a single excitation in the same elementary fibers, but rather the involvement of a various number of fibers, and that a series of processes which we have to the present attributed to the varying intensities are now to be explained by difference in the duration and form of excitation. This gives us an entirely different but nevertheless a more definite picture of the physiological character of the processes in the nervous system. Still, this question belongs to another chapter of physiology. Here we are interested in the fact that we have in the nerve a form of living substance, in which irritability has reached a high degree, and every stimulus which is at all operative brings about disintegration of all the material involved in excitation, and consequently the property of conductivity in the nerve reaches the state of highest development of all living structures, in that the medullated nerve conducts with the greatest rapidity on the one hand, and on the other, there is no decrement of the velocity and intensity of excitation. All these characteristics: the existence of the “all or none law,” the rapidity of the conduction of excitation, the absence of a decrement in the velocity, the absence of a decrement of the intensity of the excitation wave, the want of the capability of summation of excitation, are all dependent upon one another, for they are the combined expression of one and the same factor, that of the high state of irritability. When the irritability is artificially reduced, then the nerve approaches more and more, depending upon the amount of reduction, to the series of living substances in which we found the protoplasm of the rhizopoda to occupy the other extreme. Between the normal medullary nerve with its maximal, and the pseudopods of the rhizopods with their minimal capability of reaction, we find innumerable gradations in groups of living substances. Whether or not other forms of living substances follow the type of the nerve, whether for example the “all or none law” can be applied to the skeletal muscle as the investigations of Keith Lucas seem to show, requires further investigation.

Keith Lucas: “On the gradation of activity in a skeletal muscle fiber.” Journal of Physiology, Vol. IX, 1888. The same: The “all or none” contractions of the amphibian skeletal muscle-fiber. Journ. of Physiology, Vol. XXXVIII, 1909.

Finally, there arises the important question as to the finer mechanism of conductivity. The progression of excitation from cross section to cross section in a living system is brought about by the decomposition of the molecules in one region acting as a stimulus and producing a disintegration of the molecules in another region, etc. We have already seen that the intensity is dependent upon the amount of energy produced by the disintegration of the molecules following the stimulus, that is, upon the amount liberated in a definite space in a definite time. The question which now arises is this: What form of energy is produced by the stimulus at the point of stimulation, which acts upon the neighboring molecules? The conduction of excitation is a property of all living substance, and we may presume that this occurs in all living systems in the same manner. If one examines the forms of energy which are produced in a living substance by the breaking down of the molecules, we find that chiefly three forms of energy may be taken in consideration in the problem of conductivity: heat, electricity and osmotic energy. Light cannot be looked upon as a form of energy which is produced by all living substance, and the other forms of energy, as the chemical energy and surface tension, remain local. At a first glance one is inclined to assume that heat is the form of energy which is liberated by the breaking down of the stimulated molecule and which spreads to the neighboring molecules and brings about their decomposition. For we know that heat facilitates dissociation, and the analogy between living substance and explosive material is very close. In both instances the decomposition, which extends over a great mass of molecules, is accomplished by the heat produced in the breaking down of a few molecules. In fact, the conduction of excitation of a nerve can in many respects be compared with the burning of a fuse. Nevertheless, it must not be forgotten that this analogy, which on first glance seems so apt, upon closer observation presents serious difficulties. It can be experimentally shown that an increase in the temperature in the living substance follows stimulation, but it is also known that in momentary excitation following a single stimulus, as in the muscle after the application of an induction shock, the heat production is extremely small. This difficulty becomes particularly apparent if we endeavor to gain an approximate idea of the numerical proportions of the irritable, that is the disintegrating molecules to the remaining mass of a living system. The water content above all represents an enormous proportion. If we calculate this to be for the nerve, for instance, roughly about 75 per cent., which is a low estimate, only 25 per cent. of dry substances remain. Even of this 25 per cent. by far the largest part is apportioned to connective tissue, for which 15 per cent. is certainly not too high a figure. Neither can the remaining 10 per cent. of dry substances be regarded as consisting entirely of molecules capable of decomposition. For in this is also included the organic reserve material of the axis cylinder protoplasm, which is doubtless of very considerable amount. Further, the salts and products of disintegration, for which the estimate for the sum total would probably not be too low if we assume the amount to be equal to that of the group specially concerned in the process of excitation. As, however, a constant metabolism of rest takes place, these last molecules or atom groups are certainly not at the moment of entrance of the stimulus in their entirety in a condition capable of decomposition. It is quite certain, therefore, that we are still overestimating the amount of the molecules capable of disintegration, if we put them down as 5 per cent. of the entire nerve substance. If we now suppose that this 5 per cent. of irritable molecules are broken down as a result of stimulation, 95 per cent. of nonirritable substance, separating these irritable molecules, must become heated to such a degree by the disintegration of the latter that the amount of heat suffices to bring about decomposition of the nearest surrounding molecules or atom groups, for otherwise conduction of disintegration could not take place in this manner. This condition presents a serious difficulty for the assumption that heat is the form of energy responsible for the conduction of disintegration. It is true that we cannot reject this view at once as being completely incorrect, as the possibility of conduction does not depend upon the absolute amount of heat which reaches the next molecule capable of decomposition, but upon the relative amount of heat in regard to the degree of lability of the irritable molecules, of which we cannot even approximately make an estimate. However, by a comparison with other highly explosive substances, such as iodide of nitrogen, we find that a slight trace of water applied to the iodide of nitrogen suffices to prevent the extension of the disintegration process, and with this the explosion of the whole mass. Nor does the view of Pflüger remove this difficulty, which assumes that the atom groups capable of breaking down are joined together by a chemical linking of atoms to long fiber-shaped giant molecules through the whole nerve fiber, for this assumption of a firm structure can hardly be reconciled with the principles concerned of metabolism.

Compare Pflüger: “Ueber die physiologische Verbrennung in den lebendigen Organismen.” In Pflügers Archiv. Bd. 10, 1875. Further: L. Hermann: “Handbuch der Physiologie, Bd. II, Allgemeine Nervenphysiologie,” 1879.

In consideration of this difficulty it seems easier to assign the rôle of mediator of disintegration not to heat but to electricity. Production of electricity is likewise a property of all living substance. Differences of electrical potential between two points may be equalized in the stretch by conduction through the intervening space. Electricity would then fulfil the important conditions, which must be demanded for the form of energy, acting as mediator for the conduction of disintegration from cross section to cross section.

Model of a “Kernleiter.” A, B--Glass tube, with a number of side tubes filled with saline solution, through which a wire is passed. c and d--Side tubes with electrodes for stimulation. e and f--Tubes for connection with a galvanometer. (After Hermann.) ]

Physiologists even at an early date, misled by the apparent likeness in the conduction of excitation, especially in the nerve, to that of electricity in a metal wire, regarded both processes as identical. When, however, Helmholtz first demonstrated experimentally the rapidity of the conduction in the nerve, the thought that electrical conduction was concerned, such as takes place in a metal wire, had to be abandoned, as the velocity shows too great a difference in the two cases.

Scheme of the conduction by local electric currents in a “Kernleiter.” (After Hermann.)]

The observations, on the other hand, on the conductivity in the so-called “core model,” seemed to offer another possibility of attributing the conduction of excitation in the nerve to electric processes. Matteucci, later Hermann and finally Boruttau have endeavored to apply the results obtained when electricity is introduced in a wire covered with a moist envelope (saline solution), to the explanation of conductivity in the nerve. (Figure 25.) The fact has been shown, that in such a model the application of electricity to a point, as a result of polarization between the moist envelope and the metal, produces a weak local current, which in turn disturbs the electrical potential in the next cross section and consequently a new local current is produced and so on through the whole length of the wire. (Figure 26.) This fact, in connection with the apparent similarity in the differentiation of the axial fibers and peripheral envelope in the nerve, has led Boruttau to apply the principles of conductivity in the “core model” to that of the nerve. Then, however, Nernst and Zeyneck brought forward their theory, according to which the galvanic current is operative as a stimulus in that it brings about an alteration in the concentration of the ions at the junction of two different electrolites which, in turn, produce local currents. Boruttau then dropped the assumption of the existence of a simple physical polarization between the wire and the envelope and replaced it by the assumption of an alteration in the concentration of the ions at this position. Thereby the “core model explanation” was already altered in principle, in that only the differentiation of a central fibrilla and a peripheral enveloping substance was appropriated. It seems to me that this factor can likewise be considered as completely dispensable and may, therefore, be omitted; thus nothing remains of the “core model explanation” of the conduction of excitation in the nerve.

The enormously extensive literature on this subject up to the most recent date is quoted in Cremer: “Die allgemeine Physiologie der Nerven.” In Nagels Handbuch der Physiologie des Menschen, Bd. IV, 1909. Braunschweig.

The results of continually increasing numbers of investigation in recent times make it appear almost as a certainty that the elementary fibrillæ in the axis cylinder are nothing else but skeletal substances. Wolff, Verworn and others have first expressed the view that the neurofibrillæ must be looked upon as skeletal fibers for the soft neuroplasm, and more recently Lenhossek and especially Goldschmidt have confirmed this assumption in detail. Goldschmidt has shown by extensive comparative studies of cell mechanism the rôle played by the neurofibrillæ in a physical connection as internal skeletal formations, and has proved at the same time, in complete unanimity with other investigators, their continuity with other undoubted skeletal fibrillæ. By this the numerous combinations and speculations of Apathy and Bethe concerning the part taken by the neurofibrillæ have been rendered untenable. In no case is there the slightest justification to regard the apparent “Kernleiterstructur” of the nerve as the principal condition for the process of conductivity, for should we dispense completely with this point for the theory of the conduction of the nerve, we can obtain, solely by the aid of the facts known today in physical chemistry, the foundations for a theory of the conductions of excitation which not merely renders the specific case of the conduction of the nerve intelligible, but contains at the same time the principles of the process of the conduction of excitation for all living substance.

M. Wolff: “Ueber die fibrillaren Structuren in der Leber des Frosches.” Anatom. Anzeiger Bd. 26, 1905.

Max Verworn: “Bemerkungen zum heutigen Stand der Neuronlehre.” Medicin. Klinik, Jahrg. IV, 1908.

M. v. Lenhossek: “Ueber die physiologische Bedeutung der Neurofibrillen.” Anatom. Anzeiger Bd. 36, 1910.

Richard Goldschmidt: “Das Nervensystem von Ascaris lumbricoides und megalocephala. Ein Versuch in den Aufbau eines einfachen Nervensystems einzudringen.” III Teil. Festschrift zum 60 Geburtstage Richard Hertwigs Bd. II, 1910, Jena.

Scheme of the foam structure of living substance. A--In undifferentiated protoplasm. B--In fibrillae protoplasm.]

On the basis of investigation in the physical chemistry on the properties of semi-permeable membranes, we know that such membranes produce an elective effect on the diffusion of dissolved substances. This is in the way that the two different solutions, separated by a semi-permeable surface, do not follow the known laws of diffusion, but are altered in that certain substances in contrast to their rapidity of diffusion pass through the membrane or are prevented from entering by the latter. This applies likewise to the two kinds of ions, which are dissociated in diluted substances. If the surface exercises a selection in the way, for instance, that the positive kations are allowed to pass through, whilst the negative anions are held back, a difference of potential must exist between the two. In this manner, wherever two different solutions are separated from each other by a semi-permeable surface, an opportunity occurs for the taking place of galvanic currents. As we know, living protoplasm by reason of its colloidal components possesses, in common with all colloidal substances, on its surface the properties of semi-permeable membranes. Between the cell and the medium, therefore, there is always the opportunity for the occurrence of differences of electric potential. But more. We likewise know that protoplasm itself represents a mixture of colloid substances and actual solutions. Frequently, if not always, living structure presents a morphological differentiation of two types, when seen under the microscope, in the form of a foam structure described by Bütschli. (Figures 27 and 28.) If we suppose that with the disintegration of complex molecules, which we must assume as taking place in the material of the walls of the protoplasm network, substances are formed which are subjected to electrolytic dissociation, the anions and kations hereby liberated must be diffused from the place of their separation into the surroundings. Their diffusion, however, is restricted by the protoplasmic network. The positive ions may pass through, but the negative ions may not. As a result: the reticulated substance is the seat of electric discharge, which in turn gives the impact to the breaking down of new molecules and with this to the occurrence of new potential differences, and so on, consequently the disintegration is extended further and further through the connected masses of the protoplasmic framework.

Protoplasm of different cells, showing foam structures. A--Pseudopod of a marine rhizopod. The protoplasm only shows foam structure at the point of stimulation. B--Epidermic cell of lumbricus. C--Nerve fiber. D--Part of the cell body of a ganglia cell. (A-C after Bütschli, D after Held.) ]

This theory, founded on facts gained entirely from investigation, would involve those forms of energy which play the rôle of activator in the extension of the breaking down of the molecule from cross section to cross section, namely, the osmotic and the electrical energy. Based on the general properties of physical chemistry and those of morphology of the living substances, they would be applicable to all vital systems. It would be premature to attempt to extend this assumption and further develop its specific details, above all to make it responsible for the specific differences in the process of the conduction of excitation in various forms of living substance. For this our knowledge of the properties of living substance is still far too incomplete. Nevertheless, it furnishes us even now with various points of view for the further analysis of a series of vital manifestations, as, for instance, the facts concerning the production of electricity, of galvanotaxis, chemotaxis and so on. This, however, exceeds the limits of the task we have here mapped out. We are concerned here solely with the general principle on which the conductivity of excitation in the living substance is founded.