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Am J Physiol Heart Circ Physiol (December 22, 2004). doi:10.1152/ajpheart.01023.2004
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Submitted on October 7, 2004
Accepted on December 19, 2004

Localization and Modulation of Alpha1D (Cav1.3) L-type Ca Channel by Protein Kinase A

Yongxia Qu1, Ghayath Baroudi1, Yuankun Yue1, Nabil El-Sherif1, and Mohamed Boutjdir1*

1 Research and Development, VA New York Harbor Healthcare System, Brooklyn, NY, USA

* To whom correspondence should be addressed. E-mail: Mohamed.boutjdir{at}med.va.gov.

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




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