A, top view of the CaV1.1 channel with the four homologous repeats shown in different colours, using the high‐resolution cryo‐EM structure of Wu et al. (2015). B and C, side views of VSD IV models constructed of the high‐resolution cryo‐EM structure (B), and our Rosetta structure models (C), of the two splice variants with and without exon 29 (grey) (Tuluc et al. 2015). Note the overall similarity of the predicted and experimentally obtained structures. Inclusion of exon 29 slightly displaces IVS3 and IVS4 relative to each other, resulting in a channel which fails to activate during physiological depolarizations. D and F, side view structure of the channel pore. E and G, critical pore residues of the calcium selectivity filter of the rabbit channel (rb‐α1S) and the single amino acid substitutions which render the two fish CaV1.1 paralogues (zf‐α1S‐a, ‐b, medaka‐α1S‐b) non‐conductive (Schredelseker et al. 2010).