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	Rad as a novel regulator of excitation-contraction coupling and beta-adrenergic signaling in heart
	Wang, Gang2,3; Zhu, Xiaojun2; Xie, Wenjun2; Han, Peidong2; Li, Kaitao2; Sun, Zhongcui2; Wang, Yanru2; Chen, Chunlei2; Song, Ruisheng2; Cao, Chunmei2
刊名	Circulation research
	2010-02-05
卷号	106期号:2页码:317-u45
关键词	Rad Gtpase Ca(2+) signaling Excitation-contraction coupling Beta-adrenergic signaling
ISSN号	0009-7330
DOI	10.1161/circresaha.109.208272
通讯作者	Liu, jie(ljljz@yahoo.com)
英文摘要	Rationale: rad (ras associated with diabetes) gtpase, a monomeric small g protein, binds to ca(v)beta subunit of the l-type ca(2+) channel (lcc) and thereby regulates lcc trafficking and activity. emerging evidence suggests that rad is an important player in cardiac arrhythmogenesis and hypertrophic remodeling. however, whether and how rad involves in the regulation of excitation-contraction (ec) coupling is unknown. objective: this study aimed to investigate possible role of rad in cardiac ec coupling and beta-adrenergic receptor (beta ar) inotropic mechanism. methods and results: adenoviral overexpression of rad by 3-fold in rat cardiomyocytes suppressed lcc current (ica), [ca(2+)](i) transients, and contractility by 60%, 42%, and 38%, respectively, whereas the "gain" function of ec coupling was significantly increased, due perhaps to reduced "redundancy" of lcc in triggering sarcoplasmic reticulum release. conversely, approximate to 70% rad knockdown by rna interference increased i(ca) (50%), [ca(2+)](i) transients (52%) and contractility (58%) without altering ec coupling efficiency; and the dominant negative mutant rads105n exerted a similar effect on ica. rad upregulation caused depolarizing shift of lcc activation and hastened time-dependent lcc inactivation; rad downregulation, however, failed to alter these attributes. the na(+)/ca(2+) exchange activity, sarcoplasmic reticulum ca(2+) content, properties of ca(2+) sparks and propensity for ca(2+) waves all remained unperturbed regardless of rad manipulation. rad overexpression, but not knockdown, negated beta ar effects on i(ca) and ca(2+) transients. conclusion: these results establish rad as a novel endogenous regulator of cardiac ec coupling and beta ar signaling and support a parsimonious model in which rad buffers ca(v)beta to modulate lcc activity, ec coupling, and beta ar responsiveness. (circ res. 2010; 106: 317-327.)
WOS关键词	CARDIAC MYOCYTES ; CALCIUM-CHANNELS ; CA2+ RELEASE ; VENTRICULAR MYOCYTES ; RYANODINE RECEPTORS ; KINASE-II ; PHOSPHORYLATION ; SUBUNITS ; SPARKS ; MODULATION
WOS研究方向	Cardiovascular System & Cardiology ; Hematology
WOS类目	Cardiac & Cardiovascular Systems ; Hematology ; Peripheral Vascular Disease
语种	英语
出版者	LIPPINCOTT WILLIAMS & WILKINS
WOS记录号	WOS:000274258500013
内容类型	期刊论文
URI标识	http://www.corc.org.cn/handle/1471x/2414417
专题	中国科学院大学
通讯作者	Liu, Jie
作者单位	1.Shenzhen Univ, Sch Med, Dept Pathophysiol, Shenzhen 518060, Peoples R China 2.Peking Univ, Coll Life Sci, Inst Mol Med, Beijing 100871, Peoples R China 3.Peking Univ, Coll Life Sci, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100871, Peoples R China 4.Univ Michigan, Ctr Cardiovasc, Ann Arbor, MI 48109 USA
推荐引用方式 GB/T 7714	Wang, Gang,Zhu, Xiaojun,Xie, Wenjun,et al. Rad as a novel regulator of excitation-contraction coupling and beta-adrenergic signaling in heart[J]. Circulation research,2010,106(2):317-u45.
APA	Wang, Gang.,Zhu, Xiaojun.,Xie, Wenjun.,Han, Peidong.,Li, Kaitao.,...&Cheng, Heping.(2010).Rad as a novel regulator of excitation-contraction coupling and beta-adrenergic signaling in heart.Circulation research,106(2),317-u45.
MLA	Wang, Gang,et al."Rad as a novel regulator of excitation-contraction coupling and beta-adrenergic signaling in heart".Circulation research 106.2(2010):317-u45.

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