Evidence that the primary change in stimulation is an increase in the permeability of the limiting membranes of the irritable elements

Abstract

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 Larvœ of Arenicola cristata.—These are the free-swimming ciliated larvæ of a marine annelid; they are small worm-like organisms about 0.3 mm. in length, readily obtained in large quantity by rearing. The larvæ 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 larvæ are present, colors the latter a bright straw yellow. Its exit thus serves as a convenient index of increased permeability. 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 (m/2) solutions of neutral sodium salts (NaCOOCH₃, NaCl, NaBr, NaN0₃, NaCl0₃, NaI, NaCNS) all cause strong and persistent muscular contraction accompanied by rapid loss of pigment; the addition of a little calcium chloride to the solution (I C.C. m/2 CaCl₂ to 25 C.C. m/2 sodium salt) prevents both the stimulating action and the loss of pigment.