Go but not Gi2 or Gi3 is required for muscarinic regulation of heart rate and heart rate variability in mice.
Biochem Biophys Res Commun
; 357(1): 139-43, 2007 May 25.
Article
em En
| MEDLINE
| ID: mdl-17418106
ABSTRACT
Muscarinic receptor-mediated cardiac parasympathetic activity is essential for regulating heart rate and heart rate variability (HRV). It has not been clear which G(i)/G(o) protein is responsible for these effects. We addressed this question using knockout mice that lack G protein alpha(i2), alpha(i3), or alpha(o) specifically. Unlike previously reported, our alpha(o)-null mice had significantly more survivors with normal life span. Isolated hearts from alpha(o)-null mice demonstrated much less sensitivity to the negative chronotropic effects of the muscarinic agonist carbachol to lower heart rate at baseline and a more profound effect under the stimulation of the beta-adrenergic agonist isoproterenol. In the presence of parasympathetic activation indirectly produced by methoxamine, an alpha(1)-adrenergic agonist, alpha(o)-null mice showed markedly decreased HRV compared with wild-type control mice. These differences in heart rate and HRV were not observed in alpha(i2)-null or alpha(i3)-null mice. Our findings establish an essential role for alpha(o) G protein in the anti-adrenergic effect of carbachol on heart rate regulation.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Receptores Muscarínicos
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Proteínas de Ligação ao GTP
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Coração
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Frequência Cardíaca
Limite:
Animals
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article