Modulation of coronary smooth muscle KCa channels by Gs alpha independent of phosphorylation by protein kinase A.
The occupancy of beta-receptors in the smooth muscle membrane of the coronary arteries produces vasodilation and a concomitant hyperpolarization. Large conductance calcium-activated K (KCa) channels are likely to be involved in such hyperpolarization, since they are densely distributed in coronary myocytes, and they are targets of beta-adrenergic stimulation in other smooth muscles. We sought to explore if coronary smooth muscle KCa channels are modulated by beta-agonists and we studied the mechanisms of their activation. We found that KCa channels reconstituted into lipid bilayers were activated in the presence of GTP by the beta-adrenergic receptor agonist isoproterenol. KCa channels were also stimulated on non-specific activation of an endogenous G protein(s) with guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S), on addition of a purified activated stimulatory G protein (Gs alpha), and when the catalytic subunit of protein kinase A (PKA) was added. Inhibition of PKA activity prevented KCa channel stimulation by PKA, but not by endogenous G protein or by exogenous Gs alpha. These results indicate that beta-adrenoceptor activation of coronary smooth muscle KCa channels results from a dual control: 1) a membrane delimited, possibly direct action of Gs, independent of PKA-mediated phosphorylation; and 2) by PKA-dependent phosphorylation.
Scornik
F S
FS
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030.
Codina
J
J
Birnbaumer
L
L
Toro
L
L
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D003331:Coronary Vessels / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D010766:Phosphorylation; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D013552:Swine
D015221:Potassium Channels; D011943:Receptors, Adrenergic, beta; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D017868:Cyclic AMP-Dependent Protein Kinases; D019204:GTP-Binding Proteins; D002118:Calcium