the proper proportions these substances render an irritable tissue irresponsive to stimulation. I have recently found that they also change the properties of the plasma membranes in Arenicola larvæ and sea-urchin eggs in such a way as to make them more resistant to increase of permeability under the influence of salt-solutions. A definite parallelism appears to exist; if we render the membranes more resistant to alteration than formerly, we render the tissue less irritable. This influence of anesthetics on plasma-membranes is a very general if not universal characteristic of living organisms. Thus the permeability of plant-cells to salts is decreased by these substances, as Lepeschkin and Osterhout have found, and Loewe has recently shown that artificial lipoid-impregnated membranes are similarly affected. These facts explain why anesthetics counteract the effects of stimulating agencies—which cause temporary increase of permeability; and since most anesthetics are lipoid-solvents, we are led to the conclusion that they cause their effects by changing the state of the lipoid components of the membrane; thus the properties of this structure are altered—particularly the readiness with which its permeability is changed by external conditions acting upon it.
Irritability would thus appear to depend on a peculiar state of the plasma membranes—one in which under slight variations of external conditions these structures undergo automatically a rapid and pronounced increase of permeability. A certain state of physico-chemical instability or lability of the protoplasmic surface-film seems to be the essential condition on which a highly developed irritability depends. Such a membrane appears to retain its properties unaltered only if the external and internal conditions remain approximately constant, especially the state of electrical polarization. If this latter is suddenly changed, as by an external even slight electrical disturbance, some hindrance to interaction seems to be removed, and a chemical process is initiated which instantly alters the character of the membrane and stimulation follows. This, or something closely similar, appears to be the condition in tissues whose irritability is sensitive and rate of response rapid. Apparently all variations occur in the rate at which this change takes place. The electrical variation, whose rate of appearance and subsidence is an index of the rate of the surface-change, is highly rapid in some tissues and slow in others. Thus it lasts for about a thousandth of a second in a frog's motor nerve, and for several seconds in a slowly responding tissue like smooth muscle; and all intermediate conditions are known to exist. These variations in the speed and sensitivity of the response depend primarily on the specific peculiarities of the plasma membranes of the different tissues. What determines the differences between different irritable tissues and organisms in these respects is a subject for future investigation.
These peculiarities of the plasma membranes enable us to understand
