Protein kinase C activation inhibits Cav1.3 calcium channel at NH2-terminal serine 81 phosphorylation site

Protein kinase C activation inhibits Ca(v)1.3 calcium channel at NH2-terminal serine 81 phosphorylation site. Am J Physiol Heart Circ Physiol 291: H1614-H1622, 2006; doi: 10.1152/ajpheart. 00095.2006. - The Ca(v)1.3 (alpha(1D)) variant of L-type Ca2+ channels plays a vital role in the function of neuroendocrine and cardiovascular systems. In this article, we report on the molecular and functional basis of alpha(1D) Ca2+ channel modulation by protein kinase C (PKC). Specifically, we show that the serine 81 (S81) phosphorylation site at the NH2-terminal region plays a critical role in alpha(1D) Ca2+ channel modulation by PKC. The introduction of a negatively charged residue at position 81, by converting serine to aspartate, mimicked the PKC phosphorylation effect on alpha(1D) Ca2+ channel. The modulation of alpha(1D) Ca2+ channel by PKC was prevented by dialyzing cells with a 35-amino acid peptide mimicking the alpha(1D) NH2-terminal region comprising S81. In addition, the data revealed that only beta II- and epsilon PKC isozymes are implicated in this regulation. These novel findings have significant implications in the pathophysiology of alpha(1D) Ca2+ channel and in the development of PKC isozyme-targeted therapeutics.