Ions move across cell membranes through microscopic water-filled pores in large protein molecules referred to as ion channels. Such channels are characterized by their selectivity for a particular ion, mode of opening and closing - gating, and by the nature of agents that block them. This project focuses on understanding the molecular mechanisms underlying channel gating in an invertebrate model system, the giant axon from the marine worm Myxicola infundibulum, for both voltage-activated NA+ channels and voltage-activated K+ channels. In addition to using specific drugs to separate and probe ion channels function, three different electrophysiological techniques are used: (1) recording square millimeters by high-resolution, conventional voltage- clamp; (2) examining intramembrane charge movements producing the small "gating currents" that apparently initiate opening of ion channels; and (3) investigating the opening and closing of single ion channels by isolating a few square microns of the axon membrane with a glass micropipette - called "patch clamp". A full understanding of the molecular operation of ion requires the simultaneous application of all these techniques because each yields different information. Experimental results will combine with theoretical analysis to develop a detailed, testable model of ion channel function.