Barbiturates Block Sodium and Potassium Conductance Increases in Voltage-Clamped Lobster Axons

Abstract

Sodium pentobarbital and sodium thiopental decrease both the peak initial (Na) and late steady-state (K) currents and reduce the m a x i m u m 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 interactions 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.

Secobarbital Attenuates Excitotoxicity but Potentiates Oxygen—Glucose Deprivation Neuronal Injury in Cortical Cell Culture

“…At high concentra tions, barbiturates directly increase CI-conduc tance (MacDonald et aI., 1988) and block axonal Na + and K + conductances (Blaustein, 1968). In deed, electrophysiologic effects associated with high barbiturate concentrations have been proposed to be involved in producing anesthesia (Heyer and MacDonald, 1982).…”

Pentobarbitone inhibition of catecholamine secretion

“…Hypnotic derivatives of barbituric acid produce depression in a number of biological systems, including nerve axons (Schoepfle, 1957;Blaustein, 1968), ganglia (Exley, 1954;Sato, Austin & Yai, 1967), the neuromuscular junction (Thesleff, 1956;Galindo, 1971), and the monosynaptic spinal reflex arc (L0yning, Oshima & Yokota, 1964). The cellular mechanism or mechanisms responsible for this characteristic effect are not known, although several hypotheses have been formulated to explain their depressant action.…”

Proceedings of the British Pharmacological Society

“…Procaine and barbiturates are considered to have similar actions on membrane conductance changes associated with the action potential in the nerve axon (Blaustein, 1968).…”