Metabolic inhibition activates a non-selective current through connexin hemichannels in isolated ventricular myocytes.
J Mol Cell Cardiol
; 32(10): 1859-72, 2000 Oct.
Article
em En
| MEDLINE
| ID: mdl-11013130
ABSTRACT
Intracellular Na(+)accumulation and K(+)loss play important roles in the pathogenesis of arrhythmias and injury in the ischemic heart. We investigated the role of metabolically sensitive connexin hemichannels as a potential route for Na(+)influx and K(+)efflux during ischemia, using dye uptake and electrophysiological measurements to assay hemichannel activity in isolated rabbit ventricular myocytes. Consistent with the known size selectivity of connexin hemichannels,;50% of myocytes exposed to either low extracellular Ca(2+)(an established method for opening connexin hemichannels) or to metabolic inhibitors (a recently described method for opening hemichannels) accumulated fluorescent dyes with <1000 MW (propidium iodide and calcein), but excluded a larger dye with 1500-3000 MW (dextran-rhodamine). Using the whole cell patch clamp technique, we found that metabolic inhibitors activated a non-selective current permeant to both small and large cations, and blocked by La(3+), similar to the properties of connexin 43 when overexpressed in human embryonic kidney (HEK) cells. These findings indicate that isolated cardiac myocytes endogenously express metabolically-sensitive connexin hemichannels. If activated during ischemia, these hemichannels could contribute significantly to altered ionic fluxes promoting arrhythmias and myocardial injury.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácido Egtázico
/
Conexinas
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Ventrículos do Coração
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Miocárdio
Limite:
Animals
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Humans
Idioma:
En
Revista:
J Mol Cell Cardiol
Ano de publicação:
2000
Tipo de documento:
Article
País de afiliação:
Estados Unidos