Potassium channel blockers potentiate impulse inhibition by local anesthetics.

The ability of local anesthetics to reduce the amplitude of compound action potentials (CAP) of frog sciatic nerve was examined in the absence and presence of agents that selectively block K+ channels. In the presence of lidocaine concentrations that inhibit the CAP by about 20% at low frequencies of stimulation (1 per min, "tonic inhibition"), the addition of the K(+)-channel blocker tetraethylammonium ion (TEA, 12 mM) increased this inhibition by another 15%. Furthermore, the use-dependent inhibition induced by lidocaine at higher stimulation frequencies (5-20 Hz, "phasic inhibition") was markedly enhanced by TEA: at 20 Hz it increased from 35% with lidocaine alone to 63% with lidocaine plus TEA. A comparable potentiation was rendered by 3,4-diaminopyridine (1 mM), a different K(+)-channel blocker. Similarly, phasic inhibition by bupivacaine also was enhanced by TEA. The K(+)-channel blockers alone slightly depolarized the resting membrane, broadened and elevated the CAP, produced no phasic inhibition, and, during repetitive stimulation, resulted in a less negative steady-state repolarization potential than at rest. Both the broadening of CAP and the depolarizing actions of K(+)-channel blockers increased the presence of open and inactivated states of the neuronal Na+ channels, and thereby enhanced the binding of local anesthetic. The inhibitory actions of saxitoxin, a Na(+)-channel blocker that binds equally well to all channel states, were not potentiated by TEA.