Rem-GTPase regulates cardiac myocyte L-type calcium current

Janos Magyar, Carmen E. Kiper, Gail Sievert, Weikang Cai, Geng Xian Shi, Shawn M. Crump, Liren Li, Steven Niederer, Nic Smith, Douglas A. Andres, Jonathan Satin

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Rationale: The L-type calcium channels (LTCC) are critical for maintaining Ca2+-homeostasis. In heterologous expression studies, the RGK-class of Ras-related G-proteins regulates LTCC function; however, the physiological relevance of RGKLTCC interactions is untested. Objective: In this report we test the hypothesis that the RGK protein, Rem, modulates native Ca2+ current (ICa,L) via LTCC in murine cardiomyocytes. Methods and Results: Rem knockout mice (Rem-/-) were engineered, and ICa,L and Ca2+-handling properties were assessed. Rem-/- ventricular cardiomyocytes displayed increased ICa,L density. ICa,L activation was shifted positive on the voltage axis, and β-adrenergic stimulation normalized this shift compared with wild-type ICa,L. Current kinetics, steady-state inactivation and facilitation was unaffected by Rem-/-. Cell shortening was not significantly different. Increased ICa,L density in the absence of frank phenotypic differences motivated us to explore putative compensatory mechanisms. Despite the larger ICa,L density, Rem-/- cardiomyocyte Ca2+ 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 Ca2+ transients. Conclusions: This is the first demonstration that loss of an RGK protein influences ICa,L in vivo in cardiac myocytes.

Original languageEnglish
Pages (from-to)166-173
Number of pages8
JournalChannels
Volume6
Issue number3
DOIs
Publication statusPublished - Jan 1 2012

Keywords

  • Calcium current
  • L-type calcium channel
  • Patch-clamp
  • Ras-GTPase

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

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    Magyar, J., Kiper, C. E., Sievert, G., Cai, W., Shi, G. X., Crump, S. M., Li, L., Niederer, S., Smith, N., Andres, D. A., & Satin, J. (2012). Rem-GTPase regulates cardiac myocyte L-type calcium current. Channels, 6(3), 166-173. https://doi.org/10.4161/chan.20192