Figure 7.

Gene splicing producing different cysteine-rich extracellular loops in T-type channels with alternative calcium and sodium selectivities. (A) In snails, shorter exon 12a with three cysteines creates highly sodium selective T-type channels and the longer exon 12b with five cysteines generates more calcium selective T-type channels. (B) Alignment of representative species containing exon 12a/12b with conserved cysteine residues (highlighted yellow). (C) The gene tree of exon 12a/12b of T-type channels. Exon lengths are scaled with cysteine residues indicated as vertical bars. Most protostome invertebrates contain a shorter exon 12a with a three cysteines (blue) and an alternative exon 12b with five cysteines (green). All vertebrate T-type channels have exon 12a generating a single-cysteine extracellular loop. Zero or two cysteines appear in Domain II loops of cephalochordate and the most basal T-type channels (single cell coanoflagellates, placozoan, and cnidarians). Adapted from Senatore et al. (2014a).