ride solution on the pigment-containing cells of this organism; at the same time they decrease or prevent the stimulating action of this solution. They also protect the organism against its toxic action, as we have already seen. An anesthetic action is thus the equivalent of both an anti-stimulating and an anti-cytolytic action. Both effects depend upon a modification of the plasma-membrane; under the influence of the anesthetic this structure becomes more resistant than normally to conditions that otherwise increase its permeability. We may infer in general that the degree of responsiveness of an irritable tissue is dependent on the state of its plasma-membranes; and that anesthesia corresponds to a condition of decreased susceptibility, and hyper-irritability to one of increased susceptibility, to the action of permeability-increasing agencies. Sensitization and desensitization, on this view, are primarily surface effects, dependent on alteration of the limiting membranes.
The polarization-changes accompanying stimulation may be extremely rapid in some cases. During the contraction of a man's voluntary muscle under the influence of the will, the existence of a rhythmical electrical variation with an average rhythm of about fifty vibrations per second has recently been demonstrated by the thread-galvanometer. The negative variation accompanying a single muscular twitch occupies from one hundredth to one two-hundredths of a second in a frog's voluntary muscle at ordinary temperatures; that accompanying a single nerve impulse lasts about one thousandth of a second; while more slowly reacting tissues, like heart-muscle or smooth muscle, show correspondingly slower electrical variations. On the membrane-theory the corresponding permeability-changes in the membrane must occupy similar times; and this consideration indicates the extreme delicacy of the adjustment between permeability and electrical polarization that must exist in the membranes of highly irritable tissues.
The electrical phenomena of stimulation are, however, relatively inconspicuous—if we except the case of the electric eel or torpedo. The characteristic and biologically important "response" of the tissue varies with its special nature. A muscle contracts, for instance; a gland secretes. The relation between the rapid change of polarization, which is the primary event in stimulation, and the resulting mechanical and chemical effects remains to be inquired into. The problem is a difficult one, and insufficiently investigated. The energy of muscular contraction is derived from the oxidation of energy-yielding compounds, like sugar. We must conclude that the polarization-changes at the cell-surface influence the chemical processes in the muscle-cell. Stimulation is known to increase many times the rate of oxidation in muscle-cells. I have lately attempted to modify the rate of formation of indophenol (a deeply colored organic oxidation-product) in the blood cor-
