Irritability: A Physiological Analysis of the General Effect of Stimuli in Living Substance

by Max Verworn

Fig. 22.

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.

Fig. 23.

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[110] 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.

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[111] 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.