the current is broken; i. e., we obtain stimulation when the preexisting polarization of the irritable elements is rapidly diminished—in other words, when there is a depolarization. We may formulate the essential relations thus: stimulation is equivalent to depolarization, i. e., to a rapid decrease of the already existing or physiological polarization of the plasma-membranes.
Stimulation, however, is also connected with a change in the permeability of the membrane, as we have seen. We must therefore conclude—since a sudden change of polarization stimulates—that simple alteration of the electrical polarization alters the permeability of the membrane. Decrease of the potential-difference between the opposite faces of the membrane—i. e., depolarization—apparently increases permeability, and often to a remarkable degree. Irritability seems, in fact, to be an expression of this peculiar relation. The electric current thus alters the polarization of the semi-permeable membranes of the irritable tissue, and in so doing alters the permeability. This change becomes the condition of the characteristic electrical variation of the tissue; the latter is self-propagating, and thus the effects of the local stimulus are transmitted to other regions of the cell. These appear to be the essential changes in the stimulation-process as such.
According to this point of view we must conceive of the plasma-membrane of an irritable element as possessing during rest a characteristic impermeability or semi-permeability to which corresponds a definite polarization, or potential-difference between its outer and inner surfaces, of the value of (e. g.) one tenth volt. Now the permeability of the membrane is determined by a number of conditions, some of which are, its chemical composition, the temperature, the chemical changes in the protoplasm and the surroundings, and probably the state of-mechanical tension of the membrane. Another factor is, however, of fundamental importance: this is the existing state of electrical polarization of the membrane. Alteration of this polarization alters the permeability; if we decrease it we increase the permeability and stimulation may follow; if we increase it we presumably alter the permeability in the inverse direction—hence in all probability the lowered irritability at the anode (anelectrotonus) during the passage of a constant current through a muscle or nerve. Such a view ascribes peculiar properties to the plasma-membrane, but the facts lead directly to this interpretation. Girard has shown experimentally that changing the electrical polarization of a membrane of bladder or parchment alters the permeability to neutral salts. The electrical state of a membrane may thus determine its permeability. The plasma-membrane of irritable tissues has apparently acquired extreme sensitiveness to changes in its electrical polarization, such that slight electrical dis-
