Potassium channel blockers attenuate hypoxia- and ischemia-induced neuronal death in vitro and in vivo.
Stroke
; 34(5): 1281-6, 2003 May.
Article
em En
| MEDLINE
| ID: mdl-12677023
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hipóxia Encefálica
/
Isquemia Encefálica
/
Apoptose
/
Fármacos Neuroprotetores
/
Tetraetilamônio
/
Bloqueadores dos Canais de Potássio
/
Compostos de Amônio Quaternário
/
Neurônios
Limite:
Animals
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article