Potassium Channel Blockers Attenuate Hypoxia- and Ischemia-Induced Neuronal Death In Vitro and In Vivo

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Abstract
Background and Purpose— In light of recent evidence suggesting that an upregulation of K+ efflux mediated by outward delayed rectifier (IK) channels promotes central neuronal apoptosis, we sought to test the possibility that blockers of IK channels might be neuroprotective against hypoxia/ischemia-induced neuronal death. Methods— Membrane currents were recorded with the use of patch clamp recordings in cultured murine cortical neurons. Protective effects of K+ channel blockers were examined in rats subjected to transient middle cerebral artery occlusion followed by 14-day reperfusion. Results— The K+ channel blocker tetraethylammonium (TEA) (5 mmol/L) selectively blocked IK without affecting N-methyl-d-aspartate receptor–mediated current or voltage-gated Ca2+ currents. Both TEA and a lipophilic K+ channel blocker, clofilium, attenuated neuronal apoptosis induced by hypoxia in vitro and infarct volume induced by ischemia in vivo. Conclusions— These data are consistent with the idea that K+ channel–mediated...

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