| First Author | Magyar J | Year | 2012 |
| Journal | Channels (Austin) | Volume | 6 |
| Issue | 3 | Pages | 166-73 |
| PubMed ID | 22854599 | Mgi Jnum | J:309872 |
| Mgi Id | MGI:6708224 | Doi | 10.4161/chan.20192 |
| Citation | Magyar J, et al. (2012) Rem-GTPase regulates cardiac myocyte L-type calcium current. Channels (Austin) 6(3):166-73 |
| abstractText | RATIONALE: The L-type calcium channels (LTCC) are critical for maintaining Ca(2+)-homeostasis. In heterologous expression studies, the RGK-class of Ras-related G-proteins regulates LTCC function; however, the physiological relevance of RGK-LTCC interactions is untested. OBJECTIVE: In this report we test the hypothesis that the RGK protein, Rem, modulates native Ca(2+) current (I(Ca,L)) via LTCC in murine cardiomyocytes. METHODS AND RESULTS: Rem knockout mice (Rem(-/-)) were engineered, and I(Ca,L) and Ca(2+) -handling properties were assessed. Rem(-/-) ventricular cardiomyocytes displayed increased I(Ca,L) density. I(Ca,L) activation was shifted positive on the voltage axis, and beta-adrenergic stimulation normalized this shift compared with wild-type I(Ca,L). Current kinetics, steady-state inactivation, and facilitation was unaffected by Rem(-/-) . Cell shortening was not significantly different. Increased I(Ca,L) density in the absence of frank phenotypic differences motivated us to explore putative compensatory mechanisms. Despite the larger I(Ca,L) density, Rem(-/-) cardiomyocyte Ca(2+) twitch transient amplitude was significantly less than that compared with wild type. Computer simulations and immunoblot analysis suggests that relative dephosphorylation of Rem(-/-) LTCC can account for the paradoxical decrease of Ca(2+) transients. CONCLUSIONS: This is the first demonstration that loss of an RGK protein influences I(Ca,L) in vivo in cardiac myocytes. |
