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キーワード:
Brainstem; Calcium; Fura-2; Hypoxia; Medulla; Potassium channels
要旨:
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 Ca2+- 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 Ca2+ measurements in dorsal vagal neurons of rat brainstem slices. The cyanide-evoked persistent outward current was abolished by the KATP 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 Ca2+ ([Ca2+](i)) under normoxic conditions, but did not modify the rise of [Ca2+](i) associated with the cyanide-induced outward current. Cyanide depressed the SK channel-mediated afterhyperpolarizing current without changing the depolarization-induced [Ca2+](i) transient, but did not affect spike duration that is determined by BK channels. The afterhyperpolarizing current and the concomitant [Ca2+](i) rise were abolished by Ca2+-free superfusate that changed neither the cyanide-induced outward current nor the associated [Ca2+](i) increase, Intracellular BAPTA for Ca2+ chelation blocked the afterhyperpolarizing current and the accompanying [Ca2+](i) increase, but had no effect on the cyanide-induced outward current although the associated [Ca2+](i) increase was noticeably attenuated. Reproducing the cyanide-evoked [Ca2+](i) transient with the Ca2+ pump blocker cyclopiazonic acid did not evoke an outward current. Our results show that anoxia mediates a persistent hyperpolarization due to activation of KATP channels, blocks SK channels and has no effect on BK channels, and that the anoxic rise of [Ca2+](i) does not interfere with the activity of these K I channels. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved.
