Effects of isoflurane and ketamine on ATP-sensitive K channels in rat substantia nigra.

Whole cell recordings were made using midbrain slices to examine the effects of two different anaesthetics on ATP-sensitive K (K(ATP)) channels in principle neurons of rat substantia nigra pars compacta. When neurons were dialyzed with an ATP-free pipette solution during perfusion with a glucose-free external solution, a hyperpolarization and an outward current developed slowly in a tolbutamide-inhibitable manner. The volatile anaesthetic 3% isoflurane slightly depolarised the neurons in the presence of ATP in the pipette solution and glucose in the external solution, but it did not affect the hyperpolarization or outward current in response to omission of ATP and glucose. Ketamine, an intravenous anaesthetic, did not change the membrane potential when ATP and glucose were included; however, it reversibly inhibited the hyperpolarization and outward current induced by intracellular ATP depletion in a dose-dependent manner. These effects of ketamine were not mimicked by AP-5, an NMDA receptor antagonist, or indatraline, an inhibitor of catecholamine uptake. These findings suggest that these anaesthetics have no stimulatory action on K(ATP) channels in these neurons when intracellular ATP is preserved and that ketamine but not isoflurane inhibits K(ATP) channels when the channels were activated by low intracellular ATP.