Identification of a new C-terminal splice variant of CaV1.3 L-type calcium channels with unique functional properties

Abstract

Background In L-type voltage-gated calcium channels (VGCCs) the long C-terminal tail contains several sites for modulation by protein-protein interaction. CaV1.3 VGCCs (CaV1.3L) activate at negative voltages and support sinoatrial node pacemaking and hearing, and shape neuronal excitability. In CaV1.3L an intermolecular automodulatory C-terminal interaction (CTM) has been described which affects channel gating. CTM is characterized by interaction of a distal C-terminal regulatory domain (DCRD) with a more proximal regulatory domain (PCRD). If this CTM is absent as in previously described short CaV1.342A, calcium-dependent inactivation (CDI) increases and the channel activation range shifts to more negative voltages (i.e. “short” gating properties). Here we show that alternative splicing in exon 43 creates a new short splice variant CaV1.343S found in human and mouse brain. It lacks CTM, but still contains the PCRD motif, in contrast to previously described CaV1.342A. Semiquantitative PCR experiments showed that in mouse brain 39% of CaV1.3 channels contain exon 43S contrary to heart (6% 43S).