| First Author | Duan SZ | Year | 2007 |
| Journal | Biochem Biophys Res Commun | Volume | 357 |
| Issue | 1 | Pages | 139-43 |
| PubMed ID | 17418106 | Mgi Jnum | J:121785 |
| Mgi Id | MGI:3711615 | Doi | 10.1016/j.bbrc.2007.03.130 |
| Citation | Duan SZ, et al. (2007) 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 |
| abstractText | 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. |
