Differences between the actions of thiopental and pentobarbital in squid giant axons.

The action of thiopental and pentobarbital on the giant nerve fiber of the squid Doryteuthis plei under membrane potential control conditions was investigated. The effect of pentobarbital was found to be similar to that reported by other investigators, however, the replacement of the oxygen in C2 by a sulfur atom bestows excitatory properties on the molecule. Thiopental depolarizes the nerve fibers and produces spontaneous repetitive discharges. With concentrations (0.2 mM) of thiopental, the amplitude of the action potential, spontaneous or otherwise, does not change much, but its falling phase is drastically prolonged. Under voltage clamp conditions it is possible to show that either at rest or during activity the thiobarbiturate exhibits a high affinity for the potassium channels. The apparent dissociation constant of perntobarbital on sodium and potassium conductances are respectively 1.89 and 0.63 mM, whereas those of thiopental are 0.52 mM and 32.6 mM and 32.6 muM. The results also indicate that both barbiturates act as competitive synergists to suppress the increase in sodium and the potassium conductance which occurs during activity.