Protein kinase A regulates C‐terminally truncated CaV1.2 in Xenopus oocytes: roles of N‐ and C‐termini of the α1C subunit

摘要

Key points class="unordered" style="list-style-type:disc" id="tjp12274-list-0001">β‐Adrenergic stimulation enhances Ca²⁺ entry via L‐type CaV1.2 channels, causing stronger contraction of cardiac muscle cells.The signalling pathway involves activation of protein kinase A (PKA), but the molecular details of PKA regulation of CaV1.2 remain controversial despite extensive research.We show that PKA regulation of CaV1.2 can be reconstituted in Xenopus oocytes when the distal C‐terminus (dCT) of the main subunit, α1C, is truncated.The PKA upregulation of CaV1.2 does not require key factors previously implicated in this mechanism: the clipped dCT, the A kinase‐anchoring protein 15 (AKAP15), the phosphorylation sites S1700, T1704 and S1928, or the β subunit of CaV1.2. The gating element within the initial segment of the N‐terminus of the cardiac isoform of α1C is essential for the PKA effect.We propose that the regulation described here is one of two or several mechanisms that jointly mediate the PKA regulation of CaV1.2 in the heart.