Cardiac muscle and other excitable membranes must have strongly voltage-dependent conductances in order to function. The molecular basis of such conductances is unknown. Our program will investigate the voltage-dependent conductance induced by alamethicin in thin lipid membranes as a model of voltage-dependent conductances in excitable biological membranes. We will use experimental techniques capable of examining events taking place at a molecular level. We will vary temperature, composition of the aqueous bathing solutions and lipid composition of the membranes to see how they modify these events. We will evaluate the role of the primary structure of alamethicin by synthesizing analogues and characterizing their membrane effects. We hope these studies will enable us to formulate a detailed molecular picture of the action of alamethicin in bilayers. We believe such a picture will inform the attempt to reach an understanding of the molecular basis of voltage-dependent conductance in cardiac muscle membrane.