beta-Adrenergic signaling accelerates and synchronizes cardiac ryanodine   receptor response to a single L-type Ca2+ channel

doi:10.1073/pnas.0906560106

CORC > 北京大学 > 生命科学学院

	beta-Adrenergic signaling accelerates and synchronizes cardiac ryanodine receptor response to a single L-type Ca2+ channel
	Zhou, Peng ; Zhao, Yan-Ting ; Guo, Yun-Bo ; Xu, Shi-Ming ; Bai, Shu-Hua ; Lakatta, Edward G. ; Cheng, Heping ; Hao, Xue-Mei ; Wang, Shi-Qiang
刊名	proceedings of the national academy of sciences of the united states of america
	2009
关键词	beta-adrenergic receptor calcium signaling excitation-contraction coupling isoproterenol protein kinase A KINASE-A PHOSPHORYLATION PROTEIN-KINASE SARCOPLASMIC-RETICULUM HEART-FAILURE VENTRICULAR MYOCYTES CALCIUM CHANNELS SR CA2+ RELEASE MODULATION CELLS
DOI	10.1073/pnas.0906560106
英文摘要	As the most prototypical G protein-coupled receptor, beta-adrenergic receptor (beta AR) regulates the pace and strength of heart beating by enhancing and synchronizing L-type channel (LCC) Ca2+ influx, which in turn elicits greater sarcoplasmic reticulum (SR) Ca2+ release flux via ryanodine receptors (RyRs). However, whether and how beta AR-protein kinase A (PKA) signaling directly modulates RyR function remains elusive and highly controversial. By using unique single-channel Ca2+ imaging technology, we measured the response of a single RyR Ca2+ release unit, in the form of a Ca2+ spark, to its native trigger, the Ca2+ sparklet from a single LCC. We found that acute application of the selective beta AR agonist isoproterenol (1 mu M, <= 20 min) increased triggered spark amplitude in an LCC unitary current-independent manner. The increased ratio of Ca2+ release flux underlying a Ca2+ spark to SR Ca2+ content indicated that beta AR stimulation helps to recruit additional RyRs in synchrony. Quantification of sparklet-spark kinetics showed that beta AR stimulation synchronized the stochastic latency and increased the fidelity (i.e., chance of hit) of LCC-RyR intermolecular signaling. The RyR modulation was independent of the increased SR Ca2+ content. The PKA antagonists Rp-8-CPT-cAMP (100 mu M) and H89 (10 mu M) both eliminated these effects, indicating that beta AR acutely modulates RyR activation via the PKA pathway. These results demonstrate unequivocally that RyR activation by a single LCC is accelerated and synchronized during beta AR stimulation. This molecular mechanism of sympathetic regulation will permit more fundamental studies of altered beta AR effects in cardiovascular diseases.; http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000270963100076&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701 ; Multidisciplinary Sciences; SCI(E); PubMed; 26; ARTICLE; 42; 18028-18033; 106
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/162562]
专题	生命科学学院
推荐引用方式 GB/T 7714	Zhou, Peng,Zhao, Yan-Ting,Guo, Yun-Bo,et al. beta-Adrenergic signaling accelerates and synchronizes cardiac ryanodine receptor response to a single L-type Ca2+ channel[J]. proceedings of the national academy of sciences of the united states of america,2009.
APA	Zhou, Peng.,Zhao, Yan-Ting.,Guo, Yun-Bo.,Xu, Shi-Ming.,Bai, Shu-Hua.,...&Wang, Shi-Qiang.(2009).beta-Adrenergic signaling accelerates and synchronizes cardiac ryanodine receptor response to a single L-type Ca2+ channel.proceedings of the national academy of sciences of the united states of america.
MLA	Zhou, Peng,et al."beta-Adrenergic signaling accelerates and synchronizes cardiac ryanodine receptor response to a single L-type Ca2+ channel".proceedings of the national academy of sciences of the united states of america (2009).