Regulation of cardiac alternans by β-adrenergic signaling pathways
Regulation of cardiac alternans by β-adrenergic signaling pathways
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DOI：
10.1152/ajpheart.00384.2012
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发表时间：
2012-10-01
影响因子：
4.8
通讯作者：
Blatter, Lothar A.
中科院分区：
文献类型：
--
作者：
Florea, Stela M.;Blatter, Lothar A.
Florea SM, Blatter LA。肾上腺素能信号通路对心脏交替的调节。[J] .中国生物医学工程学报，2016,31(2):447 - 456。首次发表于2012年8月17日；doi: 10.1152 / ajpheart.00384.2012。在猫心房肌细胞中，β -肾上腺素能受体（β - ar）刺激对兴奋-收缩耦合和细胞Ca2+循环产生深远影响，这是由β(1)-和β (2)- ar亚型偶联到G蛋白(G（s)和G(i)）介导的。在这项研究中，我们确定了β - ar刺激对起搏诱导的Ca2+交替的影响。用荧光Ca2+指示剂indo-1记录单猫心房肌细胞的Ca2+交替。室温下，平均起搏频率为1.7 Hz时出现稳定的Ca2+交替，平均交替比为0.43。非选择性β - ar刺激以及β (1)/G(s)、β (2)/G(s) + G(i)和β (2)/G(s)偶联途径的选择性刺激均可消除起搏诱导的Ca2+交替。β (1)-AR刺激通过刺激PKA和Ca2+/钙调素依赖性蛋白激酶II来消除交替，而β (2)-AR刺激仅涉及PKA并通过G(s)介导，而已知的猫心房肌细胞中通过G(i)和一氧化氮产生的第二途径不参与交替调节。抑制各种线粒体功能（线粒体膜电位的耗散或线粒体F-1/F-0-ATP合成酶的抑制，通过线粒体Ca2+单转运体的线粒体Ca2+摄取，以及通过线粒体Na+/Ca2+交换的Ca2+挤出）增强Ca2+交替；然而，β - ar刺激仍然废除交替，只要有足够的细胞ATP可用。选择性抑制线粒体或糖酵解ATP的产生并不能阻止β - ar刺激消除Ca2+交替体。然而，当两种ATP来源都被耗尽时，β - ar刺激未能降低Ca2+交替。这些结果表明，在心房肌细胞中，β - ar刺激通过平行和互补的信号通路来防止起搏诱导的交替。
Florea SM, Blatter LA. Regulation of cardiac alternans by beta-adrenergic signaling pathways. Am J Physiol Heart Circ Physiol 303: H1047-H1056, 2012. First published August 17, 2012; doi:10.1152/ajpheart.00384.2012.-In cat atrial myocytes, beta-adrenergic receptor (beta-AR) stimulation exerts profound effects on excitation-contraction coupling and cellular Ca2+ cycling that are mediated by beta(1)- and beta(2)-AR subtypes coupled to G proteins (G(s) and G(i)). In this study, we determined the effects of beta-AR stimulation on pacing-induced Ca2+ alternans. Ca2+ alternans was recorded from single cat atrial myocytes with the fluorescent Ca2+ indicator indo-1. Stable Ca2+ alternans occurred at an average pacing frequency of 1.7 Hz at room temperature with a mean alternans ratio of 0.43. Nonselective beta-AR stimulation as well as selective stimulation of beta(1)/G(s), beta(2)/G(s) + G(i), and beta(2)/G(s) coupled pathways all abolished pacing-induced Ca2+ alternans. beta(1)-AR stimulation abolished alternans through stimulation of PKA and Ca2+/calmodulin-dependent protein kinase II, whereas beta(2)-AR stimulation exclusively involved PKA and was mediated via G(s), whereas a known second pathway in cat atrial myocytes acting through G(i) and nitric oxide production was not involved in alternans regulation. Inhibition of various mitochondrial functions (dissipation of the mitochondrial membrane potential or inhibition of mitochondrial F-1/F-0-ATP synthase, mitochondrial Ca2+ uptake via the mitochondrial Ca2+ uniporter, and Ca2+ extrusion via mitochondrial Na+/Ca2+ exchange) enhanced Ca2+ alternans; however, beta-AR stimulation still abrogated alternans, provided that sufficient cellular ATP was available. Selective inhibition of mitochondrial or glycolytic ATP production did not prevent beta-AR stimulation from abolishing Ca2+ alternans. However, when both ATP sources were depleted, beta-AR stimulation failed to decrease Ca2+ alternans. These results indicate that in atrial myocytes, beta-AR stimulation protects against pacing-induced alternans by acting through parallel and complementary signaling pathways.