The overall objective is elucidation of the mechanism of ion permation through excitable membranes, and an understanding of the molecular basis of gating phenomena. Experiments are to be performed on internally perfused giant axons of the squid, subjected to voltage clamps. Specific areas of study are: the mechanism by which foreign ions and drugs block current through the ionic channels; the interaction of drugs and ions with the gating machinery of the channels; the characteristics of gating currents associated with the ionic channels; and means by which ionic channels may be specifically labeled covalently.