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Barbiturates Block Sodium and Potassium Conductance Increases in Voltage-Clamped Lobster Axons M. P. BLAUSTEIN From the Naval Medical Research Institute, Bethesda, Maryland 20014. Dr. Blausteins present address is Department of Physiology, Cambridge University, England ABSTRACT Sodium pentobarbital and sodium thiopental decrease both the peak initial (Na) and late steady-state (K) currents and reduce the maximum sodium and potassium conductance increases in voltage-clamped lobster giant axons. These barbiturates also slow the rate at which the sodium conductance turns on, and shift the normalized sodium conductance vs. voltage curves in the direction of depolarization along the voltage axis. Since pentobarbital (pK, = 8.0) blocks the action potential more effectively at pH 8.5 than at pH 6.7, the anionic form oi the drug appears to be active. The data suggest that these drugs affect the axon membrane directly, rather than secondarily through effects on intermediary metabolism. It is suggested that penetration of the lipid layer of the membrane by the nonpolar portion of the barbiturate molecules may cause the decrease in membrane conductances, while electrostatic inter- actions involving the anionic group on the barbiturate, divalent cations, and fixed charges in the membrane could account for the slowing of the rate of sodium conductance turn-on and the shift of the normalized conductance curves along the voltage axis. INTRODUCTION It is now well-established that the local anesthetic, procaine, blocks the nerve action potential by reducing both the early transient (Na) and late steady- state (K) conductance increases in the isolated peripheral nerve fiber (Taylor, 1959; Shanes et al., 1959; and Blaustein and Goldman, 1966 a). Similar effects are observed in the perfused squid axon whether procaine is applied