THE THEORY OF AN/ESTHESIA. 353 



which sensitive organisms like protozoa show to the contact 

 stimuli of food particles or prey; also in the prompt response of 

 many living cells to the presence of substances which are known 

 from experiments on permeability not to penetrate the plasma- 

 membranes. In general these membranes in their normal state 

 are impermeable to the neutral salts of the alkali and alkali 

 earth metals, as Overton showed; yet variations in the pro- 

 portions of such salts in the tissue-media profoundly influence 

 the activity and irritability of living cells. Increase in the 

 magnesium or calcium salts of the medium may cause typical 

 anaesthesia in muscle and . nerve cells. Warburg and Harvey 1 

 have shown that cell-division in sea-urchin eggs may be arrested 

 by weak solutions of sodium hydrate without the alkali pene- 

 trating the cell. A. J. Clark has made similar observations for 

 heart muscle cells, and Harvey for the contractile cells of medusae 

 and for protoplasmic rotation in plant-cells. 2 Irritability and 

 automatic activity may thus be abolished by substances to 

 which the" cell-surface is impermeable. The general facts of 

 electrical stimulation also indicate that alteration in the electrical 

 condition of the cell-surface is the primary event in stimulation. 

 The investigations of Nernst and his successors in the theory of 

 electrical stimulation show that the electrical current stimulates 

 by changing the relative concentrations of ions on the opposite 

 faces of the semi-permeable membranes enclosing the irritable 

 elements, i. e., by altering the electrical polarization of the 

 surface-film or the plasma-membrane. A characteristic electrical 

 variation, the action-current which is best explained as the 

 result of alterations in the electromotor properties of the cell 

 surface also accompanies all forms of stimulation, and this 

 electro-motor variation is prevented by anaesthetics. It may 

 be held, therefore, with a high degree of probability that the 

 primary event in stimulation is a surface-process, consisting in 

 some physico-chemical alteration of the modified protoplasmic 

 surface-film (plasma-membrane) which delimits irritable cells. 3 



1 Warburg, loc. cit.; E. N. Harvey, Journ. Exper. Zoo/., 1911, Vol. 10, p. 507. 



2 A. J. Clark, Journ. Physiol., 1913, Vol. 46, p. xx; Vol. 47, p. 66; E. N. Harvey, 

 loc. cit., and Yearbook of Carnegie Institution, No. 10, 1911, p. 128. 



3 For a general discussion of the evidence bearing on this problem cf. my article 

 "The Relation of Stimulation and Conduction in Irritable Tissues to Changes in 



