MEMBRANES AND CELL-PROCESSES 143 



prevented. The same effect may be produced by various anesthetics; 

 these also protect the cells against the permeability-increasing action of 

 the ra/2NaCl, 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 w/2NaCl, neither stimula- 

 tion nor loss of pigment follows. The same is true if they are brought 

 from ether-containing sea-water into ether-containing m/2NaCl; and 

 other anesthetics in appropriate concentrations show a similar inhibi- 

 tory 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 solu- 

 tions. 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 anti- 

 toxic as well as an anti-stimulating action. 



It is impossible within the limits of this article adequately to dis- 

 cuss the physiology of stimulation. A few of its aspects ought, how- 

 ever, 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 sensi- 

 tivity 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 precon- 

 ception 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, hoAvever, to 

 inquire more particularly into the nature and conditions of the response 

 of irritable tissues to the electrical current, and of the electrical proc- 

 esses originating in the tissues themselves, and to relate these processes, 

 if possible, to the total effects produced by stimulation. 



