Rapid beta-adrenergic modulation of cardiac calcium channel currents by a fast G protein pathway.
beta-Adrenergic agonists activate the G protein, Gs, which stimulates cardiac calcium currents by both cytoplasmic, indirect and membrane-delimited, direct pathways. To test whether beta-adrenergic agonists might use both pathways in the heart, isoproterenol was rapidly applied to cardiac myocytes, resulting in a biphasic increase in cardiac calcium channel currents that had time constants of 150 milliseconds and 36 seconds. beta-Adrenergic antagonists of a G protein inhibitor blocked both the fast and slow responses, whereas the adenylyl cyclase activator forskolin produced only the slow response. The presence of a fast pathway in the heart can explain what the slow pathway cannot account for: the ability of cardiac sympathetic nerves to change heart rate within a single beat.
Yatani
A
A
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030.
Brown
A M
AM
D000818:Animals; D016275:Atrial Function; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D015398:Signal Transduction
D015220:Calcium Channels; D005576:Colforsin; D002217:Carbachol; D019204:GTP-Binding Proteins; D007545:Isoproterenol