cAMP-dependent phosphorylation of the cardiac L-type Ca channel: A missing link?

摘要

Cardiac inotropic effects of β adrenergic agonists occur mainly through an increase in L-type (class C) calcium channel activity. This response has been attributed to phosphorylation of the L-type Ca channel, or a closely associated protein, by the cAMP-dependent protein kinase A (PKA). Among the three subunits forming the cardiac L-type Ca channel (α1, β and α2-δ), biochemical studies have revealed that two subunits, α1 and β, are phosphorylated in vitro by protein kinase A, the α1 subunit being the primary target. However, attempts to reconstitute the cAMP-dependent regulation of the expressed class C Ca channel, either in Xenopus oocytes or in cell lines, have provided contradictory results. We were unable to detect cAMP-dependent modulation of class C α1 subunit Ca channels expressed in Xenopus oocytes, even when coinjected with auxiliary subunits β and α2-δ. Nevertheless, activity of Ca channels recorded from cardiac-mRNA injected oocytes was potentiated by injection of cAMP or PKA, even when expression of the β subunit was suppressed using antisense oligonucleotide. Taken together, these results indicate that cAMP-dependent regulation does not exclusively involve the α1 and the β subunits of the Ca channel and suggest that unidentified protein(s), expressed in cardiac tissue, are most likely necessary.