Heart rate regulation by G proteins acting on the cardiac pacemaker channel.
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.
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030.
A
A
Yatani
K
K
Okabe
J
J
Codina
L
L
Birnbaumer
A M
AM
Brown
D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D002474:Cell-Free System; D004553:Electric Conductivity; D019204:GTP-Binding Proteins / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D006339:Heart Rate; D066298:In Vitro Techniques; D007473:Ion Channels / Q000502:physiology*; D011817:Rabbits; D011941:Receptors, Adrenergic / Q000502:physiology; D011976:Receptors, Muscarinic / Q000502:physiology; D012849:Sinoatrial Node / Q000502:physiology*; D013873:Thionucleotides / Q000494:pharmacology
D007473:Ion Channels; D011941:Receptors, Adrenergic; D011976:Receptors, Muscarinic; D013873:Thionucleotides; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins