| First Author | Chen F | Year | 2001 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 280 |
| Issue | 5 | Pages | H1989-95 |
| PubMed ID | 11299198 | Mgi Jnum | J:69295 |
| Mgi Id | MGI:1934424 | Doi | 10.1152/ajpheart.2001.280.5.H1989 |
| Citation | Chen F, et al. (2001) Lack of muscarinic regulation of Ca(2+) channels in G(i2)alpha gene knockout mouse hearts. Am J Physiol Heart Circ Physiol 280(5):H1989-95 |
| abstractText | The purpose of the present study was to examine the role of G(i2)alpha in Ca(2+) channel regulation using G(i2)alpha gene knockout mouse ventricular myocytes. The whole cell voltage-clamp technique was used to study the effects of the muscarinic agonist carbachol (CCh) and the beta-adrenergic agonist isoproterenol (Iso) on cardiac L-type Ca(2+) currents in both 129Sv wild-type (WT) and G(i2)alpha gene knockout (G(i2)alpha-/-) mice. Perfusion with CCh significantly inhibited the Ca(2+) current in WT cells, and this effect was reversed by adding atropine to the CCh-containing solution. In contrast, CCh did not affect Ca(2+) currents in G(i2)alpha-/- ventricular myocytes. Addition of CCh to Iso-containing solutions attenuated the Iso-stimulated Ca(2+) current in WT cardiomyocytes but not in G(i2)alpha-/- cells. These findings demonstrate that, whereas the Iso-G(s)alpha signal pathway is intact in G(i2)alpha gene knockout mouse hearts, these cells lack the inhibitory regulation of Ca(2+) channels by CCh. Therefore, G(i2)alpha is necessary for the muscarinic regulation of Ca(2+) channels in the mouse heart. Further studies are needed to delineate the possible interaction of G(i) and other cell signaling proteins and to clarify the level of interaction of G protein-coupled regulation of L-type Ca(2+) current in the heart. |
