Modulation of calcium channel function by phosphorylation in guinea pig ventricular cells and phospholipid bilayer membranes.

L-type calcium channel activity of some excitable cells is markedly enhanced by beta-adrenergic agents. The enzymatic cascade underlying this important modulatory effect has been studied with patch-clamp techniques in single dialyzed ventricular cells from guinea pig heart. The steps between the binding of agonist to the beta-receptor and the increase in calcium influx can be summarized as follows: Agonist binding to beta-receptor greater than adenylate cyclase increases greater than cAMP increases greater than cA-kinase increases greater than protein phosphorylation greater than altered calcium channel properties greater than ICa increases A basal phosphorylation reaction seems not to be a prerequisite for calcium channel function. By combining molecular and functional approaches, the purified dihydropyridine-receptor complex from rabbit skeletal muscle transverse-tubules can be reconstituted in phospholipid bilayer membranes to form a functional 20-pS calcium channel that retains the principal regulatory, biochemical, and pharmacologic properties of membrane-bound L-type calcium channels.