First Author | Ye CP | Year | 2008 |
Journal | Am J Physiol Heart Circ Physiol | Volume | 294 |
Issue | 2 | Pages | H979-85 |
PubMed ID | 18156202 | Mgi Jnum | J:132363 |
Mgi Id | MGI:3775849 | Doi | 10.1152/ajpheart.00293.2007 |
Citation | Ye CP, et al. (2008) G(o) controls the hyperpolarization-activated current in embryonic stem cell-derived cardiocytes. Am J Physiol Heart Circ Physiol 294(2):H979-85 |
abstractText | Hyperpolarization current (I(f)) is an important player in controlling heart rate and is stimulated by cAMP and inhibited by members of the pertussis toxin-sensitive G-protein G(i)/G(o) family. We have successfully derived cardiocytes from embryonic stem cells lacking G(o) or G(i2) and G(i3). We have established that both basal and isoproterenol-stimulated activities of I(f) in these cardiocytes have typical nodal-atrial characteristics and are unaffected by targeted gene inactivation of the G proteins G(o) or G(i2) and G(i3). Under basal conditions, both G(o) and G(i) are required for muscarinic inhibition of I(f) activity via a mechanism that involves the generation of nitric oxide, whereas, with prior stimulation by beta-agonists, only G(o) is required and G(i) and nitric oxide production are not. Our findings establish an essential role for G(o) in the antiadrenergic effect of muscarinic agent on I(f). |