Published Online
on April 3, 2003

A more recent version of this article appeared on May 1, 2003

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Submitted on November 21, 2002
Accepted on November 21, 2002

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

Ling Wei MD; Shan Ping Yu MD, PhD; Frank Gottron PhD; B. Joy Snider MD, PhD; Gregory J. Zipfel MD; and Dennis W. Choi MD, PhD^*

From the Center for the Study of Nervous System Injury and Department of Neurology, Washington University School of Medicine, St Louis, Mo.

^* To whom correspondence should be addressed. E-mail: wildersp{at}neuro.wustl.edu.

Background and Purpose--In light of recent evidence suggesting that an upregulation of K⁺ efflux mediated by outward delayed rectifier (I_K) channels promotes central neuronal apoptosis, we sought to test the possibility that blockers of I_K 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 I_K 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 K⁺ efflux may contribute to ischemia-triggered apoptosis and suggest that preventing excessive K⁺ efflux through K⁺ channels may constitute a therapeutic approach for the treatment of stroke.

Key words: hypoxia • ischemia • middle cerebral artery occlusion • tetraethylammonium

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