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

by Max Verworn

Although the nerve as an isobolic system can only be rendered capable of exhibiting summation when artificially influenced, there are other forms of living substance which normally are systems with a slow course of excitation, in which excitation may be summated, for this type possesses at the same time a heterobolic character. For example, a single mechanical excitation elicits a hardly perceptible response in Amœba, Actinosphærium, Orbitolites. When it is perceptible at all, there occurs a short interruption of the centrifugal movement of the protoplasm. After a pause the movement of the protoplasm and the stretching out of the pseudopods again return. But if the organism is agitated one or more minutes by rhythmically shaking the edge of the slide by a special device, as a result of the summation of weak excitations there occurs a complete drawing in of the pseudopods and the amœbæ become bell-shaped.[187] The ganglion cells also possess a great capability for summation. We have already alluded to the fact that single induction shocks below that of the threshold produce no evident effect, whereas when rapidly repeated, summation occurs with reflex reaction.

Fig. 54.

Development of tonus by interference of sub-threshold stimuli. S—Level of the threshold of perceptible effect.

The summation of sub-threshold excitation to a certain height offers very favorable conditions for the development of tonus. (Figure [54].) This fact has been established for many kinds of centers (cardio-inhibitory center, vasomotor center, etc.). During the continuance of a series of stimuli, as we have already seen, an equilibrium between disintegration and replacement soon takes place. The level of this state of equilibrium depends upon the relative intensity of the stimuli. It is lower in the case of strong and higher in that of weak stimuli. This fact becomes apparent from the researches of Thörner[188] on the fatigue of medullated nerves in air. This investigator showed that during continued tetanic stimulation of the nerve, the irritability fell to a certain level, at which it remained so long as stimulation persisted. The irritability decreased to a new level when the strength of the stimulus was increased. These interesting experiments of Thörner show that the level reached when stimulation is continued is higher as the intensity is weaker. It is, therefore, clear that this level in summation of stimulation beneath the threshold can be above that of the threshold of perceptible response, that is, a perceptible tonic excitation may result. In the genesis of tonus in the muscle, there is another point to be taken into consideration. Here we have a combination of a heterotopic interference with a homotopic interference, for the total shortening of the muscle is brought about in part by several contraction waves which occur at various points at the same time and which follow each other, therefore have a heterotopic sequence. If we consider a long stretch of muscle, to one end of which a stimulus is applied, it will be found that the contraction wave moves throughout the entire length. If after a certain interval of time a second stimulus is applied, the resultant wave moves along the muscle but does not necessarily homotopically interfere with the first. In short, there are two waves of contraction occurring coincidently in the muscle, the muscle is now more strongly contracted. Fröhlich[189] has made the fact intelligible by this means that tetanic shortening of a muscle is greater than that of maximal shortening which can be produced by strong single stimulation. This heterotopic interference dare not be overlooked in the genesis of muscle tonus. If it is true, as appears from the investigations of Keith Lucas,[190] that the “all or none law” applies to striated muscle, then an increase of the contraction from homotopic summation cannot occur, because an isobolic system cannot show an increase of its already maximal excitation by summation. Such being the case, the tonic shortening of striated muscle can only be explained as an expression of a heterotopic interference.

If we assume that the summation of sub-threshold stimulation, by increasing excitation, brings about a state of equilibrium from below, as it were, so also inhibition may be assumed to be the reverse, the level of equilibrium being reached from above, as it were, by decrease of the primary excitation from strong stimulation. This is expressed in our general scheme of the development of summation and inhibition resulting from the effect of a series of stimuli. At the same time the first part of the curve to the fall of irritation to the level of the sub-threshold equilibrium can be shortened to a minimum by strong stimulation or greater frequency of the same, and we have then the type of inhibition with primary excitation. As example of this I wish to again recall the strychninized frog which was used in the fundamental experiments for understanding of the theory of inhibition. If we stimulate a sensory nerve of a strychninized frog, in which the refractory period is already lengthened, with rhythmic single induction shocks of slow frequency, the muscle arranged to make a graphic record will show reflex contraction following each stimulus. If, on the other hand, we apply a series of stimuli, consisting of single stimuli rapidly repeated, contraction is produced only by the first, or the first few stimuli (Figures [45] and [46], pages 202, 203). For the succeeding stimuli the centers remain inhibited, because each succeeding stimulus occurs in the refractory period of the former. The origin of this inhibition shows us with particular clearness how excitation produced by each single stimulus depending upon the frequency of the same, falls rapidly or slowly beneath the threshold of perceptible response. In this case, the state of equilibrium is reached which is maintained by the following stimuli. That a single stimulus is not entirely without effect upon this state of equilibrium follows from the fact that during the continuation of the stimulus a recovery to the point of observable response does not occur, whereas such is the case immediately upon the discontinuation of the stimulus. In inhibition, then, the dissimilatory excitation produced by a single stimulus falls to a low level as a result of the reduction of irritability and remains at this level continuously. Inhibition as well as tonus is based upon the development of a state of equilibrium between excitation and recovery, or disintegration and restitution of the living substance under the continuous effect of a rhythmic series of stimuli. They differentiate themselves essentially by the height of this equilibrium, which is dependent upon the intensity of the stimulus.

We have to the present considered only the simplest conditions existing as a result of the effect of a single series of stimuli and also of the interference of its individual members. These elementary conditions are at the basis of an understanding of complicated interference effects which arise when two series of stimuli interact. In that these processes can be readily explained by the elementary processes previously described, I will, therefore, dwell but briefly on this subject. From the standpoint already taken it may be readily presumed what will happen when two series of stimuli act upon the same system.

When there is interference of two series of stimuli, there are two resultant possibilities. In one type the stimuli of the one are active simultaneously with that of the other. In this instance both stimuli would act as a single stimulus of greater intensity, and we have essentially the same condition as exists when a single series is operative. Nevertheless, such cases are practically hardly realized in the physiological happenings of the organism. More often a state exists wherein the single stimuli of one series occur in the intervals of the stimuli of the other. In these cases there is an increase in the frequency of the stimuli applied in a given length of time. We have here, then, in principle the same conditions as when a series of greater frequency is operative. (Figure [55].) The effect of such alteration in the frequency consists in an increase of the velocity of the development of summation or inhibition, as the general scheme (Figure [55]) has shown us. Depending upon the special combination of the factors involved in interference, we may have a summation of the exciting effect of each series of stimuli or an inhibition of one series by the exciting effects of the other series. If the frequency of both series is essentially different, we may have here the conditions for periodically increasing and decreasing excitations. Nevertheless these conditions have not been systematically analyzed and experimentally studied.

Fig. 55.