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This Article Full Text Full Text (PDF) All Versions of this Article: 288/5/H2123    most recent 01023.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (17) Citing Articles via Google Scholar Google Scholar Articles by Qu, Y. Articles by Boutjdir, M. Search for Related Content PubMed PubMed Citation Articles by Qu, Y. Articles by Boutjdir, M.

Localization and modulation of _1D (Cav1.3) L-type Ca channel by protein kinase A

Veterans Affairs New York Harbor Healthcare System, State University of New York Downstate Medical Center, Brooklyn and New York School of Medicine, New York, New York

Submitted 7 October 2004 ; accepted in final form 19 December 2004

_1D L-type Ca channel was assumed to be of neuroendocrine origin only; however, _1D L-type Ca channel knockout mice exhibit sinus bradycardia and atrioventricular block, indicating a distinct role of _1D in the heart. The presence and distribution of _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 _1D L-type Ca channel in rabbit and rat hearts and its modulation by PKA. Here, we show the exclusive presence of _1D Ca channel transcript in the sinoatrial node, atrioventricular node, and atria but not in the ventricle by RT-PCR and the expression of _1D Ca channel protein in atrial myocytes' sarcolemma by indirect immunostaining and Western blot. There is no significant difference in the expression level of _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 _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 _1D Ca channel protein. The results are first to demonstrate that PKA phosphorylation of L-type Ca channel _1D-subunit resulted in an increase of the _1D Ca channel activity. Together with the observation that _1D Ca channel is exclusively present in the sinoatrial node and atria, the findings suggest that _1D Ca channel plays a unique role in the sinoatrial tissue and is a target for sympathetic control of heart rhythm.

phosphorylation; protein kinase A; sinoatrial node

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