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Science 7 September 1990:
Vol. 249. no. 4973, pp. 1163 - 1166
DOI: 10.1126/science.1697697
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Articles

Science, Vol 249, Issue 4973, 1163-1166
Copyright © 1990 by American Association for the Advancement of Science

articles

Heart rate regulation by G proteins acting on the cardiac pacemaker channel

A Yatani, K Okabe, J Codina, L Birnbaumer, and AM Brown

Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030.

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.


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