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Channels (Austin). November 2, 2017; 11 (6): 604-615.

Protein kinase C enhances plasma membrane expression of cardiac L-type calcium channel, Ca V 1.2.

Raifman TK , Kumar P , Haase H , Klussmann E , Dascal N , Weiss S .

L-type-voltage-dependent Ca 2+ channels (L-VDCCs; Ca V 1.2, α 1C ), crucial in cardiovascular physiology and pathology, are modulated via activation of G-protein-coupled receptors and subsequently protein kinase C (PKC). Despite extensive study, key aspects of the mechanisms leading to PKC-induced Ca 2+ current increase are unresolved. A notable residue, Ser1928, located in the distal C-terminus (dCT) of α 1C was shown to be phosphorylated by PKC. Ca V 1.2 undergoes posttranslational modifications yielding full-length and proteolytically cleaved CT-truncated forms. We have previously shown that, in Xenopus oocytes, activation of PKC enhances α 1C macroscopic currents. This increase depended on the isoform of α 1C expressed. Only isoforms containing the cardiac, long N-terminus (L-NT), were upregulated by PKC. Ser1928 was also crucial for the full effect of PKC. Here we report that, in Xenopus oocytes, following PKC activation the amount of α 1C protein expressed in the plasma membrane (PM) increases within minutes. The increase in PM content is greater with full-length α 1C than in dCT-truncated α 1C , and requires Ser1928. The same was observed in HL-1 cells, a mouse atrium cell line natively expressing cardiac α 1C , which undergoes the proteolytic cleavage of the dCT, thus providing a native setting for exploring the effects of PKC in cardiomyocytes. Interestingly, activation of PKC preferentially increased the PM levels of full-length, L-NT α 1C . Our findings suggest that part of PKC regulation of Ca V 1.2 in the heart involves changes in channel''s cellular fate. The mechanism of this PKC regulation appears to involve the C-terminus of α 1C , possibly corroborating the previously proposed role of NT-CT interactions within α 1C .

PubMed ID: 28901828
PMC ID: PMC5786194
Article link: Channels (Austin).

Bauer, 1999, Pubmed[+]

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