Potassium channel blockers attenuate hypoxia- and ischemia-induced neuronal death in vitro and in vivo.

Abstract

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.

• Authors: Ling Wei, Shan Ping Yu, Frank Gottron, B Joy Snider, Gregory J Zipfel, Dennis W Choi
• Journal: Stroke (Stroke) Vol. 34 Issue 5 Pg. 1281-6 (May 2003) ISSN: 1524-4628 [Electronic] United States
• PMID: 12677023 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Calcium Channels
• Culture Media
• Neuroprotective Agents
• Potassium Channel Blockers
• Quaternary Ammonium Compounds
• Receptors, N-Methyl-D-Aspartate
• Tetraethylammonium
• clofilium
• Glucose
• Potassium
• Calcium

Topics

• Animals
• Apoptosis (drug effects)
• Brain Ischemia (drug therapy, pathology)
• Calcium (metabolism)
• Calcium Channels (metabolism)
• Calcium Signaling (drug effects)
• Carotid Artery, Common
• Cell Hypoxia (drug effects)
• Cells, Cultured (drug effects, pathology)
• Cerebral Cortex (cytology)
• Culture Media (pharmacology)
• Drug Evaluation, Preclinical
• Glucose (pharmacology)
• Hypoxia, Brain (drug therapy, pathology)
• Infarction, Middle Cerebral Artery (complications, drug therapy, pathology)
• Ion Transport (drug effects)
• Ligation
• Male
• Mice
• Middle Cerebral Artery
• Neurons (drug effects, pathology)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Patch-Clamp Techniques
• Potassium (metabolism)
• Potassium Channel Blockers (pharmacology, therapeutic use)
• Quaternary Ammonium Compounds (pharmacology)
• Rats
• Receptors, N-Methyl-D-Aspartate (drug effects, physiology)
• Tetraethylammonium (pharmacology)