Interaction of lidocaine with the cardiac sodium channel: effects of low extracellular pH are consistent with an external blocking site.
Life Sci
; 67(22): 2759-66, 2000 Oct 20.
Article
em En
| MEDLINE
| ID: mdl-11105992
ABSTRACT
Brief extracellular application of millimolar concentrations of lidocaine affected sodium currents recorded in isolated rat ventricular myocytes in two ways 1) a reduction of the maximum current consistent with a channel blocking action, and 2) a negative shift in the voltage dependence of inactivation consistent with an interaction with the inactivated state of the channel. Both effects occurred very rapidly (<< 1 s). Decreasing extracellular pH to 6.4 increased the potency for channel block (EC50 1.8 +/- 0.2 mM at pH 7.4 and 0.8 +/- 0.1 mM at pH 6.5) and decreased the potency to shift inactivation (V(1/2) shift -42 mV by 1 mM lidocaine at pH 7.4 and -12.6 mV at pH 6.5). Channel block was slightly less at +90 mV compared to -40 mV at either pH (not statistically significant). The increase in potency for block at decreased extracellular pH, while intracellular pH is buffered, and the lack of voltage dependence of block, suggest that the charged form of lidocaine can block the channel by interacting with a site near the extracellular mouth, although alternative explanations are discussed.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Bloqueadores dos Canais de Sódio
/
Potenciais Evocados
/
Coração
/
Concentração de Íons de Hidrogênio
/
Lidocaína
Limite:
Animals
Idioma:
En
Revista:
Life Sci
Ano de publicação:
2000
Tipo de documento:
Article