Localization and modulation of α 1D (Cav1.3) L-type Ca channel by protein kinase A

α 1D L-type Ca channel was assumed to be of neuroendocrine origin only; however, α 1D L-type Ca channel knockout mice exhibit sinus bradycardia and atrioventricular block, indicating a distinct role of α 1D in the heart. The presence and distribution of α 1D Ca channel in the heart and its regulation by protein kinase A (PKA) are just emerging. Our objective was to examine the localization of α 1D L-type Ca channel in rabbit and rat hearts and its modulation by PKA. Here, we show the exclusive presence of α 1D Ca channel transcript in the sinoatrial node, atrioventricular node, and atria but not in the ventricle by RT-PCR and the expression of α 1D Ca channel protein in atrial myocytes' sarcolemma by indirect immunostaining and Western blot. There is no significant difference in the expression level of α 1D Ca channel in the left versus right atrium. Superfusion of membrane-permeable 8-bromo-cAMP resulted in a significant increase of the peak current density of α 1D Ca current expressed in tsA201 cells. This increase was inhibited by the PKA inhibitor (PKI). Application of 8-bromo-cAMP also readily phosphorylated the α 1D Ca channel protein. The results are first to demonstrate that PKA phosphorylation of L-type Ca channel α 1D -subunit resulted in an increase of the α 1D Ca channel activity. Together with the observation that α 1D Ca channel is exclusively present in the sinoatrial node and atria, the findings suggest that α 1D Ca channel plays a unique role in the sinoatrial tissue and is a target for sympathetic control of heart rhythm.