title: Rem-GTPase regulates cardiac myocyte L-type calcium current.
abstract: BACKGROUND
  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.
  
  
  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 β-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.
authors.affiliation: Department of Physiology, University of Kentucky College of Medicine, Lexington, USA.
authors.forename: Janos
authors.initials: J
authors.lastname: Magyar
authors.forename: Carmen E
authors.initials: CE
authors.lastname: Kiper
authors.forename: Gail
authors.initials: G
authors.lastname: Sievert
authors.forename: Weikang
authors.initials: W
authors.lastname: Cai
authors.forename: Geng-Xian
authors.initials: GX
authors.lastname: Shi
authors.forename: Shawn M
authors.initials: SM
authors.lastname: Crump
authors.forename: Liren
authors.initials: L
authors.lastname: Li
authors.forename: Steven
authors.initials: S
authors.lastname: Niederer
authors.forename: Nic
authors.initials: N
authors.lastname: Smith
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Andres
authors.forename: Jonathan
authors.initials: J
authors.lastname: Satin
mesh_terms: D000200:Action Potentials / Q000235:genetics; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D005260:Female; D006352:Heart Ventricles / Q000166:cytology; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D020559:Monomeric GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D018408:Patch-Clamp Techniques
chemical_list: D020746:Calcium Channels, L-Type; D020559:Monomeric GTP-Binding Proteins; C576618:Rem1 protein, mouse; D002118:Calcium