Mechanism of blockade of neuromuscular transmission by pentobarbital.

The mechanism of block of neuromuscular transmission by pentobarbital has been studied in the frog sciatic nerve-sartorius muscle preparation by means of intracellular microelectrode and voltage clamp techniques. The resting membrane potential was decreased by pentobarbital only to a small extent (less than 15 mV) in both end-plate and non-end-plate regions. Both sodium and potassium components of end-plate current underwent drastic changes after application of pentobarbital. The peak amplitude was decreased with an apparent dissociation constant of 0.9 mM for both currents. The maximum rate of rise of end-plate current was reduced, with apparent dissociation constants of 0.9 and 1.2 mM for sodium and potassium currents, respectively. The times for sodium and potassium end-plate current to reach their peaks were shortened only to a negligible extent. The falling phase of end-plate current was greatly accelerated, sodium current being affected more than potassium current. The transient end-plate depolarization induced by iontophoretic application of acetylcholine was suppressed more effectively than end-plate potential by application of pentobarbital. The falling phase of the former was also shortened. The quantal content of end-plate potential tended to increase at 0.5 mM, but underwent no appreciable change at 1.0 and 1.4 mM. Pentobarbital has a dual action on both quantal content and end-plate membrane depending on the concentration, and the block of neuromuscular transmission is due primarily to a suppression of the end-plate sensitivity to acetylcholine. The differential effect of pentobarbital on sodium and potassium components of end-plate current is compatible with the notion that these two ionic conductances are separate entities.