prevented. The same effect may be produced by various anesthetics; these also protect the cells against the permeability-increasing action of the , and at the same time prevent stimulation. Thus, if Arenicola larvae are exposed for a few minutes to an isotonic solution of a magnesium salt and are then brought into , neither stimulation nor loss of pigment follows. The same is true if they are brought from ether-containing sea-water into ether-containing ; and other anesthetics in appropriate concentrations show a similar inhibitory and protective action. These and similar experiments point to the conclusion that a membrane-alteration, in the direction of rapid increase of permeability, is constantly associated with stimulation. It is of course apparent that such increase in permeability must in normal stimulation be perfectly reversible. If the reversibility is incomplete, permanent injury results; and this is in fact the case when Arenicola larva? are stimulated by immersion in pure isotonic sodium salt solutions. We have already seen that this injurious action, as well as the stimulating action, is greatly diminished by the presence of calcium chloride, or some other antitoxic salt. Anesthetics also show an antitoxic as well as an anti-stimulating action.
It is impossible within the limits of this article adequately to discuss the physiology of stimulation. A few of its aspects ought, however, to be touched on here, since otherwise the above relation between permeability-increase and stimulation may appear as a merely empirical or detached observation, without any general or theoretical significance. The most striking physical peculiarity of irritable tissues is their sensitivity to electrical changes in their surroundings. Most persons are accustomed to think of electrical currents as laboratory phenomena par excellence, and as playing little part in nature outside of laboratory walls. Yet living cells are profoundly influenced by such currents. We can in fact imitate the normal conditions more closely by using electrical currents as stimuli, than in any other manner. This preconception is however a completely mistaken one. Not only do irritable tissues respond to electrical currents, but certain electrical changes in the tissues themselves are invariably associated with stimulation, whether normal or artificial, and form perhaps the most constant and essential feature of the stimulation-process. Such a statement may sound like a truism to any one versed even slightly in modern physical chemistry: ions—charged molecules and atoms—are present everywhere in protoplasm, and it would perhaps be surprising if electrical changes did not accompany protoplasmic activities. We have, however, to inquire more particularly into the nature and conditions of the response of irritable tissues to the electrical current, and of the electrical processes originating in the tissues themselves, and to relate these processes, if possible, to the total effects produced by stimulation.
