A mouse model to study the C-terminal regulation of CaV1.3 L-type calcium channels

Background CaV1.3 voltage-gated L-type Ca 2+ channels (LTCCs) play an important role for hearing, cardiac pacemaking and neuronal excitability. The C-terminus of CaV1.3 tightly controls channel gating by an intramolecular protein interaction involving two putative a-helices (termed PCRD, DCRD), which form a C-terminal modulatory mechanism (CTM) only in full-length CaV1.3 variants. In short (CaV1.342A and CaV1.343S) CaV1.3 a1 subunit splice variants CTM is absent which leads to profound changes in channel gating: activation occurs at more negative voltages and Ca-dependent inactivation (CDI) is faster.