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

by Max Verworn

Finally, there is another factor to be considered, namely, that the latent period of the second stimulus is more and more prolonged as the second stimulus approaches more closely to the absolute refractory period of the first. In the above schemes the latent period was not taken into consideration because practically for all the intervals of stimulation considered at that time it could be assumed to be the same. When, however, a decrease of the intervals between the individual stimuli takes place, the prolongation of the latent period can then not be overlooked, as it leads to a retardation of response. (Figures [29], [30].) This fact was shown in the classic investigations of Marey[177] upon the refractory period of the heart, and more recently has been the subject of study by Samojloff,[178] Keith Lucas[179] and Gotch[180] in the muscle and nerve. These, then, are the essential factors which bring about interference, and although there are special details which deserve more close analysis, nevertheless, we are in a position to attribute to them the origins of summation and inhibitory processes, which occur in all living systems, especially the nervous system.

For the analysis of summation and the inhibitory processes which occur in the physiologically active organisms or which are experimentally produced, a very important point should be observed, that is, the fact that the stimuli which bring about these phenomena are practically always a series of single stimuli. The nerve impulses, for example, consist of a shorter or a longer series of single discharges which follow each other in rapid rhythmic sequence. Here, then, we have the conditions necessary for the production of interference effects when these single stimuli follow each other with sufficient frequency and also when there is the combined action of two series.

Fig. 53.

Curve showing the general development of the effect produced by interference of the stimuli of the same series in an heterobolic system. The effect is first summation and then inhibition. R indicates the intensity of the stimuli, S the level of the threshold of perceptible effect.

We will first direct our attention to the simplest case brought about by an interference between the individual effects of stimuli in the same series. We will study the effect, which here occurs, in the accompanying diagram, which shows the facts involved in the interference of two stimuli of a series of stimuli. (Figure [53].) The curve shows the development of summation and inhibition. The single stimuli of equal intensity follow at the same intervals, so that the succeeding stimuli meet with an incomplete recovery of excitation and accordingly a decreased state of irritability. In spite of the diminution of the relative response to each stimulus the summation of excitation brings about an absolute increase of the same. At the same time the irritability decreases more and more, for after each stimulation the oxydative disintegration as well as restitution require a progressively greater time and a relative fatigue must, therefore, necessarily develop. The summation, consequently, reaches its limit very soon and then decreases progressively, for, as a result of the increase of fatigue, the oxydative decomposition which occurs at the instant of every stimulation reduces and with this the energy production becomes less and less. The system is relatively refractory for the given intensity of stimulus. Accordingly the response to stimulation falls below the threshold of perceptible response (dotted line S) and finally an equilibrium between disintegration and restitution occurs, wherein the small amount of material used at each stimulation by oxydative decomposition is again replaced before the next stimulus. In other words, the irritability is reduced at each stimulation to an amount equal to that of the recovery in the interval. If this all takes place beneath the threshold of perceptible response, the system during the continuance of the stimulation seems responseless, that is, inhibited. The inhibition consists then of a reduction of irritability below the perceptible threshold of response of the stimulus concerned. It depends upon a continued lessening of dissimilative excitation to a low level through the delay of the oxydative decomposition processes. The inhibition is according to this a relative fatigue, which is conditioned, as is true of every fatigue, by a lengthening of the refractory period following a relative deficiency of oxygen. The processes of inhibition are simply and solely an expression of a refractory period persisting as a result of dissimilatory excitating stimuli.

Accordingly the general conditions requisite for summation on the one side and inhibition on the other may be formulated as follows:

A summation may develop in a heterobolic system and by the use of submaximal stimuli. It always develops when the following stimulus is applied before there is complete recovery of excitation from the previous stimulus. The absolute increase of excitation as a result of summation is, however, limited by the diminution of irritability. By continuation of the series of stimuli the state of equilibrium between the amount of excitation and the irritability will be established on a higher or lower level. There occurs then, depending on whether the feeble persistent excitation remains above or below the level of perceptible effect, either a tonus or an inhibition.

Summation can be transformed into inhibition by the continuance of stimuli of constant intensity. The principles which underlie both processes are in no way antagonistic and indeed are not separated by distinct boundaries. The diagram here shown (Figure [53]) illustrates this development of summation and inhibition. The time required for this development is in manifold ways influenced by variations of the above-stated factors which control the occurrence of interference. Thereby results an immense number of special cases which differentiate themselves in characteristic manner depending on whether an isobolic or heterobolic system is involved, depending on whether the irritability of the system, as measured by the threshold of stimulation, is high or low, depending on whether fatigability is great or small, depending upon the intensity and frequency of the stimuli, etc. Analysis of every instance shows us different combinations of the interaction of the individual factors. It is, therefore, self-evident that we cannot here analyze a greater number of these cases of summation and inhibition. I wish only to refer to a few typical examples at this time.

It is known that summation of excitation in the normal nerve does not occur. As already stated, the nerve is a system in which the “all or none law” is operative. Such isobolic systems do not summate, having no power of summation because each individual stimulus brings about a maximum response. But we have seen that the nerve, as a result of depressing factors, such as deficiency of oxygen, narcosis, fatigue, etc., which decrease its irritability, can be transformed from an isobolic into a heterobolic system. In this state the nerve possesses the capability of summating excitations. Waller,[181] Boruttau,[182] Boruttau and Fröhlich,[183] Thörner[184] and others have shown that the action current of the nerve during the application of tetanic stimulation becomes decidedly greater during a certain stage of narcosis or asphyxiation, so that the wave of negative variation is higher than when the nerve is excitated by a single induction shock. Fröhlich[185] first threw light upon this subject in that he made the observation that here a principle is involved which has far-reaching importance in the phenomena occurring in the organism. He showed that as a result of fatigue, cold and narcosis, etc., the course of excitation brought about by the single stimulation undergoes retardation. These conditions within certain limits become more favorable for the production of summation, because each succeeding stimulus meets with a more incomplete recovery of excitation than the one previously applied. In consequence of this, the irritability of the system in the beginning of fatigue, or narcosis, or immediately after the application of cold, is apparently increased. This “apparent excitation,” as it was called by Fröhlich, depends, however, in reality upon a beginning depression which is evident in that the course of the individual excitations are lengthened by this means. The irritability is likewise also reduced. Reinecke[186] later studied in further detail the retardation of excitation in the muscle and attributed to this the characteristic property shown in muscle in the so-called “reaction of degeneration.” Fatigue, asphyxia, cold, degeneration, in fact all factors which retard the course of excitation, are favorable to the summation of excitation, provided their influence does not exceed certain limits.