MEMBRANES AND CELL-PROCESSES 149 



turbances in the surroundings may lead to a large increase of per- 

 meability, and hence to marked stimulation. 1 



On this hypothesis we can also understand why the state of excita- 

 tion is transmitted from one region of the irritable element to another. 

 It is highly probable that the effect of a local stimulation is propagated 

 over the surface of the muscle-cell or nerve-fiber because of the elec- 

 trical variation which the permeability-change at the excited region 

 itself produces. This electrical variation affects the adjacent regions 

 of the membrane, and alters their permeability, with corresponding 

 electrical effects, and so the effect spreads. The explanation of the 

 conduction-process in a nerve or other irritable tissue is on this view 

 identical with that of the stimulation-process. There is, in fact, good 

 evidence that the region in a state of excitation simply excites the 

 adjoining regions electrically by means of its action-current, and that 

 the effect is transmitted in essentially this manner. 



It is possible to change the polarization of the membrane, and 

 hence its permeability, in other ways than by passing an electrical 

 current. Or we may alter the permeability directly, by acting on the 

 cell by chemical substances, or by suddenly changing the temperature, 

 or by mechanical action. When such treatment produces a sufficient 

 increase of permeability, we may suppose that all ions become free to 

 pass the membrane, and that a polarization-change then occurs, with 

 consequent stimulation which, like other forms of stimulation, is self- 

 propagating. On such a view the ordinary forms of mechanical and 

 chemical stimuli are at bottom electrical in their nature. Such stimuli 

 act by directly altering the permeability of the membrane and hence 

 its electrical polarization. 



On the other hand, the properties of the membrane may be so modi- 

 fied under certain conditions that it fails to respond to changes of 

 polarization by changes in its permeability. This occurs, for instance, 

 in narcosis. I have found that narcotics, in the concentrations at 

 which they anesthetize the musculature of Arenicola larvae, also check 

 or prevent the permeability-increasing action of isotonic sodium chlo- 



1 The assumption of a permeability-increase at the time of stimulation 1 is 

 the only hypothesis, so far as I know, that accounts at once for the two charac- 

 teristic and invariable accompaniments of stimulation, (1) the negative electrical 

 variation, and (2) the temporary loss of irritability (refractory period) during 

 the electrical variation. The time-relations of these two outwardly diverse phe- 

 nomena coincide, as Tait has shown, and both are to be regarded as expressions 

 or consequences of the same change, namely, a temporary increase in the per- 

 meability of the limiting membranes. This increase involves a temporary loss of 

 the semi-permeability which is essential to the maintenance of the normal polar- 

 ization of the membrane, and also — according to Nernst's theory — essential to 

 electrical stimulation. I therefore regard the existence of a refractory period 

 as furnishing strong support to the general theory of stimulation and conduction 

 outlined above. 





