Yatani A, Okabe K, Codina J, Birnbaumer L, Brown A M
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030.
Science. 1990 Sep 7;249(4973):1163-6. doi: 10.1126/science.1697697.
Heart rate is determined by pacemaker currents, of which the most important is the hyperpolarization-activated current I(f). Heart rate and I(f) are increased by beta-adrenergic agonists and decreased by muscarinic agonists released from cardiac sympathetic and vagal nerves, respectively. The hypothesis that the receptors for each agonist are directly coupled to I(f) channels by G proteins was tested. Under substrate-free conditions, preactivated G protein Gs stimulated and preactivated G protein G(o) inhibited I(f) channels of sinoatrial node pacemaker cells. These effects were mimicked by the corresponding preactivated alpha subunits of the G proteins. Unexpectedly, the two G proteins acted simultaneously, with G(o) being the more potent. This result may explain in molecular terms the classical observation in cardiac physiology, that vagal inhibition of heart rate is much greater on a background of sympathetic stimulation.
心率由起搏电流决定，其中最重要的是超极化激活电流I(f)。心率和I(f)分别因β-肾上腺素能激动剂而增加，因心脏交感神经和迷走神经释放的毒蕈碱激动剂而降低。对每种激动剂的受体通过G蛋白直接与I(f)通道偶联的假说进行了测试。在无底物条件下，预激活的G蛋白Gs刺激而预激活的G蛋白Go抑制窦房结起搏细胞的I(f)通道。这些效应被G蛋白相应的预激活α亚基模拟。出乎意料的是，这两种G蛋白同时起作用，其中Go的作用更强。这一结果可能从分子角度解释了心脏生理学中的经典观察结果，即在交感神经刺激的背景下，迷走神经对心率的抑制作用要强得多。
