Mechanism of action of ketamine in the current and voltage clamped myelinated nerve fibre of the frog.
The effects of the general anaesthetic ketamine, on the frog isolated node of Ranvier, were studied under current and voltage clamp conditions. Ketamine (0.5 and 1 mM) reversibly decreased the amplitude of the action potential and increased both the duration of the action potential and the threshold potential. When the K current was blocked, spontaneous action potentials appeared after washout of the drug. Ketamine rapidly blocked the Na current and more slowly modified a fraction of Na channels (about 10%) to give rise to a non-inactivatable (late) Na current. After washout of the drug, the block reversed more rapidly than the ketamine-induced late Na current disappeared. Steady-state outward, peak Na and ketamine-induced late Na currents were rapidly and reversibly blocked by ketamine with an apparent dissociation constant of 0.7 mM. Both peak Na and ketamine-induced late Na currents were reversibly blocked by procaine.
E
E
Benoit
M R
MR
Carratù
J M
JM
Dubois
D
D
Mitolo-Chieppa
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D007649:Ketamine / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009413:Nerve Fibers, Myelinated / Q000187:drug effects*; D011343:Procaine / Q000494:pharmacology; D011893:Rana esculenta; D012964:Sodium / Q000502:physiology
D007473:Ion Channels; D011343:Procaine; D007649:Ketamine; D012964:Sodium