Before going back to the cases of inhibition and explaining them by this general principle, it is necessary that we penetrate more deeply into the details of the characteristic course of the refractory period. By this means we will find the conditions which universally determine the interference in the effects of stimulation.
First of all, it is self-evident that the occurrence of interference of stimulation in a living system can only take place when the succeeding stimulus is applied before the effects of the previous one have completely disappeared. Within the interval, however, which is involved from the moment of the beginning of a stimulus until its effect disappears through the self-regulation of metabolism, there is the possibility of various interference results from stimulation.
If we take into consideration the various instances which can arise, perhaps we may best start with that type wherein the first stimulation produces depression, whereas the second has an exciting effect on disintegration. In this type the response to the second stimulus is weaker than when the second stimulus alone is applied. As a concrete example of this type, we may refer to the interference of an induction shock in a nerve during the relative want of oxygen. We arrange a nerve of a nerve muscle preparation of a frog in a glass chamber, as already described, and determine the threshold of stimulation of the stretch within the chamber by the weakest induction shocks which produce response. The oxygen is then removed and the effect on the threshold determined. As shown by Baeyer it is found that with increasing asphyxia the threshold of stimulation for induction shocks becomes continually higher. The irritability is likewise decreased. This occurs, as the investigations of Lodholz show, at first slowly, then more and more rapidly. The curve of the decrease of irritability has a logarithmic form. During the continuation of the depressing stimulus, i.e., the want of oxygen, the exciting stimulus has less and less effect. If oxygen is again brought in contact with the nerve, irritability immediately returns to its original height. The cessation of the depressing stimulus has, therefore, the effect that the exciting stimulus again brings about its original response.
A second type of interference is produced when both stimuli bring about depression. As an example, we may select the interference of cold and deficiency of oxygen. If we assume, for instance, that each of these stimuli of itself brings about only a partial reduction of living processes and not a complete suppression, then it would be possible to think of a summation of both depressions. Nevertheless, the conditions for the summation of depression have never been carefully analyzed. Quantitative investigations upon the interference of depressing stimuli are entirely lacking. One should not, however, in physiology presuppose what may happen under certain given conditions without first making the necessary experiments. The strength of scientific investigation depends upon the fact that every deduction, no matter how small, must be substantiated by experience before further progress can be made. So, likewise, we must await the results of thorough experimentation upon the interference of depressing stimuli before we can establish a law. The conditions are not as simple as they appear on first observation, for the point of attack of the various kinds of the depressing stimuli upon the chain of metabolic processes may be very different. In such a case it is not at once possible to understand the results of the interference.
There is a third type in which two dissimilatory excitations interfere with each other. Fortunately there is a great amount of experimental data at our command so that today we have a clear understanding of the essential points of the conditions necessary for the development of summation of excitation on the one hand, and inhibition on the other. If we take an instance of a momentary dissimilatory excitation operating upon an aërobic system in metabolic equilibrium, it is necessary to recall the two effects thereby produced. The stimulus brings about an oxydative decomposition of the living substance. Likewise there is a reduction of irritability. Both of these alterations are the foundation of interference. Both processes have a specific time of occurrence. The disintegration, determined by energy production, reaches a maximum suddenly, then diminishes, at first rapidly, then more and more slowly until the zero point is reached. In an analogous manner the irritability abruptly reaches a minimum, then increases rapidly, then more slowly, until it again reaches its previous value. When we represent these processes by a curve, they assume the following form. (Figure [47].) In this diagram the abscissa is the time, the ordinate value zero is the level of the metabolism of rest and the specific irritability. The points above the abscissa represent disintegration, that is, energy production, those under the abscissa, the reduction of irritability. A consideration of the latent period may be omitted. At the end of the curve the effect of stimulation may be assumed to have disappeared and the state of metabolic equilibrium reestablished. If we base our further observations upon this curve of excitation, we can study in them the factors upon which responsivity is dependent when a second exciting stimulus is operative during the course of the first.
Fig. 47.
Fig. 48.
