title: Potassium channel blockers potentiate impulse inhibition by local anesthetics.
abstract: 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.
authors.affiliation: Anesthesia Research Laboratories, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: D
authors.initials: D
authors.lastname: Drachman
authors.forename: G
authors.initials: G
authors.lastname: Strichartz
mesh_terms: D015761:4-Aminopyridine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000077770:Amifampridine; D000818:Animals; D002045:Bupivacaine / Q000494:pharmacology*; D007552:Isotonic Solutions / Q000494:pharmacology; D008012:Lidocaine / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects* / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects*; D011892:Rana catesbeiana; D000077331:Ringer's Solution; D012584:Sciatic Nerve / Q000187:drug effects / Q000502:physiology; D012996:Solutions; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology*
chemical_list: D007552:Isotonic Solutions; D015221:Potassium Channels; D012996:Solutions; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D000077331:Ringer's Solution; D008012:Lidocaine; D015761:4-Aminopyridine; D000077770:Amifampridine; D002045:Bupivacaine