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(Stroke. 2003;34:1281.)
© 2003 American Heart Association, Inc.

Original Contributions

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 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.

Correspondence to Dr Dennis Choi, Department of Neurology, Box 8111, 660 S Euclid Ave, Washington University Medical School, St Louis, MO 63110. 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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