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001-es BibID:BIBFORM037325
Első szerző:Magyar János (élettanász)
Cím:Rem-GTPase regulates cardiac myocyte L-type calcium current / 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.
Dátum:2012
Megjegyzések: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 (ICa,L) via LTCC in murine cardiomyocytes. Methods and Results: Rem knockout mice (Rem (-/-) ) were engineered, and ICa,L and Ca ( 2+) -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 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 ICa,L in vivo in cardiac myocytes.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
monomer G-protein
heart
calcium channel
Megjelenés:Channels 6 : 3 (2012), p. 166-173. -
További szerzők:Kiper, Carmen E. Sievert, Gail Cai, Weikang Shi, Geng-Xian Crump, Shawn M. Li, Liren Niederer, Steven Smith, Nic Andres, Douglas Satin, Jonathan
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
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