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

by Max Verworn

Fig. 24.

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.

Fig. 24.

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[112] seem to show, requires further investigation.

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.[113] 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.

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.