The long-range purpose of this project is to study the function and structure of membrane ionic channels and their interaction with drugs. We have determined the effects of tetraethylammonium (TEA) and quinidine on the Myxicola giant axon. TEA works on both the internal and external membrane surfaces. The primary effect of quinidine is to block potassium channels, and this action may explain its usefulness as an antiarrhythmic agent. We have also determined the effects of tetrodotoxin and local anesthetics on tisse-cultured cells. Charged and uncharged local anesthetics act at different sites in the sodium channel.