L型电压依赖性钙通道α(1)亚基在转基因小鼠中的心脏特异性过表达。异丙肾上腺素诱导的收缩功能丧失。
Cardiac-specific overexpression of the alpha(1) subunit of the L-type voltage-dependent Ca(2+) channel in transgenic mice. Loss of isoproterenol-induced contraction.
作者信息
Muth J N, Yamaguchi H, Mikala G, Grupp I L, Lewis W, Cheng H, Song L S, Lakatta E G, Varadi G, Schwartz A
机构信息
Institute of Molecular Pharmacology and Biophysics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.
出版信息
J Biol Chem. 1999 Jul 30;274(31):21503-6. doi: 10.1074/jbc.274.31.21503.
The L-type voltage-dependent calcium channel (L-VDCC) regulates calcium influx in cardiac myocytes. Activation of the beta-adrenergic receptor (betaAR) pathway causes phosphorylation of the L-VDCC and that in turn increases Ca(2+) influx. Targeted expression of the L-VDCC alpha(1) subunit in transgenic (Tg) mouse ventricles resulted in marked blunting of the betaAR pathway. Inotropic and lusitropic responses to isoproterenol and forskolin in Tg hearts were significantly reduced. Likewise, Ca(2+) current augmentation induced by iso- proterenol and forskolin was markedly depressed in Tg cardiomyocytes. Despite no change in betaAR number, isoproterenol-stimulated adenylyl cyclase activity was absent in Tg membranes and NaF and forskolin responses were reduced. We postulate an important pathway for regulation of the betaAR by Ca(2+) channels.
L型电压依赖性钙通道（L-VDCC）调节心肌细胞中的钙内流。β-肾上腺素能受体（βAR）途径的激活导致L-VDCC磷酸化，进而增加Ca(2+)内流。L-VDCC α(1)亚基在转基因（Tg）小鼠心室中的靶向表达导致βAR途径明显减弱。Tg心脏对异丙肾上腺素和福斯高林的变力性和变时性反应显著降低。同样，Tg心肌细胞中由异丙肾上腺素和福斯高林诱导的Ca(2+)电流增强也明显受到抑制。尽管βAR数量没有变化，但Tg细胞膜中异丙肾上腺素刺激的腺苷酸环化酶活性缺失，且对NaF和福斯高林的反应降低。我们推测Ca(2+)通道对βAR的调节存在一条重要途径。
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