Permeability of Membranes of Irritable Elements. 89 
53 (578) 
Evidence that the primary change in stimulation is an increase 
in the permeability of the limiting membranes 
of the irritable elements. 
By RALPH S. LILLIE. 
[From the Marine Biological Laboratory, Woods Hole, and the 
Physiological Laboratory, Zoological Department, University 
of Pennsylvania.] 
Various facts and theoretical considerations indicate clearly 
that the process of stimulation in muscle or nerve has its seat 
at the semi-permeable boundary layers or plasma membranes 
of the irritable elements, and consists in a sudden and reversible 
increase in the permeability of these membranes. After a brief 
review of this general evidence the following experiments were 
described. 
I. Experiments with the Larva of Arenicola cristata. — These 
are the free-swimming ciliated larvae of a marine annelid ; they are 
small worm-like organisms about 0.3 mm. in length, readily 
obtained in large quantity by rearing. The larvae have a well- 
developed muscular system; the special peculiarity which fits 
them for the purpose of the following experiments is the presence 
throughout the whole body of a water-soluble yellow pigment; 
this substance is contained within the cells, and does not visibly 
leave the latter except under conditions of markedly increased 
permeability — as on death or after treatment with cytolytic 
substances (e. g., saponin); it then diffuses into the medium and, 
if sufficient larvae are present, colors the latter a bright straw yellow. 
Its exit thus serves as a convenient index of increased permea- 
bility. It was found that during strong chemical stimulation 
a rapid loss of pigment always occurs : the rate and degree of this 
loss run closely parallel with the intensity of the stimulating action, 
as indicated by the extent and duration of the muscular shortening. 
Pure isotonic {ml 2) solutions of neutral sodium salts (NaCOOCH 3 , 
NaCl, NaBr, NaN0 3 , NaC10 3 , Nal, NaCNS) all cause strong 
and persistent muscular contraction accompanied by rapid loss 
of pigment; the addition of a little calcium chloride to the solution 
(1 c.c. m/2 CaCl 2 to 25 c.c. m/2 sodium salt) prevents both the 
