THE THEORY OF AN/ESTHESIA. 365 



of the dependent electrical polarization are induced by external 

 agencies. Slight permeation of the lipoids with a lipoid-solvent 

 apparently often facilitates such changes, and hence increases 

 irritability; the present of more lipoid-solvent renders a change 

 of permeability difficult, hence the protective or anaesthetic 

 action; while concentrated solutions of lipoid-solvents disrupt 

 the membrane and produce cytolytic or irreversible alterations 

 in the cells; hence such substances in higher concentrations are 

 markedly toxic." 1 



The question of just how this stabilizing influence is exerted is 

 the critical one. An irritable element like a nerve-fiber or muscle- 

 cell responds to a slight local electrical stimulation or mechanical 

 impact; this response is apparently associated with a rapid and 

 reversible increase of membrane-permeability; to this latter 

 change the electrical variation is apparently due. It is this 

 membrane-change, with the associated variation of electrical 

 polarization, which appears to be the primary physiological 

 event in stimulation; it spreads rapidly over the whole mem- 

 brane, and the other consequences of stimulation (contraction, 

 increased oxidation, etc.) follow upon this surface-change. The 

 question thus involves the whole problem of the physiology of 

 stimulation. This is not the place for a detailed discussion of 

 the various questions implicated in this central problem. It is 

 evident, however, that the whole process of stimulation depends 

 on the local initiation of the excitation-state, and on the rapid 

 conduction of this state from the point of stimulation so as to 

 affect the entire element. 2 All of these processes depend on the 

 physical and chemical condition of the membrane; hence altering 

 this condition alters the whole stimulation-process. 



According to this conception the sensitivity of the membrane 

 to changes of electrical polarization is its most characteristic 

 peculiarity. 3 The basis of this sensitivity remains to be deter- 



1 BIOLOGICAL BULLETIN, 1911, Vol. 22, p. 328; cf. p. 331. 



2 For a more special discussion of the conditions of conduction, as distinguished 

 from the other features of the stimulation process, cf. my two recent papers in 

 the Amer. Journ. Physiol., 1914, Vol. 34, p. 414, and 1915, Vol. 37, p. 348. 



3 Cf. the concluding section of my paper on antagonisms between salts and 

 anaesthetics, Amer. Journ. Physiol., 1912, Vol. 29, p. 391 seq. "In anaesthesia 

 it is to be assumed that the membrane is so altered that it fails to respond to a 

 change in its electrical polarization by an increase in its permeability" (p. 393 ) 



