Chemical anoxia activates ATP-sensitive and blocks Ca(2+)-dependent K(+) channels in rat dorsal vagal neurons in situ.
The contribution of subclasses of K(+) channels to the response of mammalian neurons to anoxia is not yet clear. We investigated the role of ATP-sensitive (K(ATP)) and Ca(2+)-activated K(+) currents (small conductance, SK, big conductance, BK) in mediating the effects of chemical anoxia by cyanide, as determined by electrophysiological analysis and fluorometric Ca(2+) measurements in dorsal vagal neurons of rat brainstem slices. The cyanide-evoked persistent outward current was abolished by the K(ATP) channel blocker tolbutamide, but not changed by the SK and BK channel blockers apamin or tetraethylammonium. The K(+) channel blockers also revealed that ongoing activation of K(ATP) and SK channels counteracts a tonic, spike-related rise in intracellular Ca(2+) ([Ca(2+)](i)) under normoxic conditions, but did not modify the rise of [Ca(2+)](i) associated with the cyanide-induced outward current. Cyanide depressed the SK channel-mediated afterhyperpolarizing current without changing the depolarization-induced [Ca(2+)](i) transient, but did not affect spike duration that is determined by BK channels. The afterhyperpolarizing current and the concomitant [Ca(2+)](i) rise were abolished by Ca(2+)-free superfusate that changed neither the cyanide-induced outward current nor the associated [Ca(2+)](i) increase. Intracellular BAPTA for Ca(2+) chelation blocked the afterhyperpolarizing current and the accompanying [Ca(2+)](i) increase, but had no effect on the cyanide-induced outward current although the associated [Ca(2+)](i) increase was noticeably attenuated. Reproducing the cyanide-evoked [Ca(2+)](i) transient with the Ca(2+) pump blocker cyclopiazonic acid did not evoke an outward current. Our results show that anoxia mediates a persistent hyperpolarization due to activation of K(ATP) channels, blocks SK channels and has no effect on BK channels, and that the anoxic rise of [Ca(2+)](i) does not interfere with the activity of these K(+) channels.
Kulik
A
A
II. Physiologisches Institut, Universität Göttingen, Germany.
Brockhaus
J
J
Pedarzani
P
P
Ballanyi
K
K
D018528:ATP-Binding Cassette Transporters; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002614:Chelating Agents / Q000494:pharmacology; D003486:Cyanides / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D005260:Female; D007004:Hypoglycemic Agents / Q000494:pharmacology; D002534:Hypoxia, Brain / Q000378:metabolism* / Q000503:physiopathology; D054086:KATP Channels; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D017208:Rats, Wistar; D051640:Small-Conductance Calcium-Activated Potassium Channels; D019789:Tetraethylammonium / Q000494:pharmacology; D014044:Tolbutamide / Q000494:pharmacology; D014630:Vagus Nerve / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D018528:ATP-Binding Cassette Transporters; D002614:Chelating Agents; D003486:Cyanides; D007004:Hypoglycemic Agents; D054086:KATP Channels; D051036:Large-Conductance Calcium-Activated Potassium Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D024661:Potassium Channels, Inwardly Rectifying; D051640:Small-Conductance Calcium-Activated Potassium Channels; C092520:uK-ATP-1 potassium channel; D001030:Apamin; D019789:Tetraethylammonium; D014044:Tolbutamide; D002118:Calcium