Conserved biophysical features of the Ca(V)2 presynaptic Ca(2+) channel homologue from the early-diverging animal Trichoplax adhaerens

The dominant role of Ca(V)2 voltage-gated calcium channels for driving neurotransmitter release is broadly conserved. Given the overlapping functional properties of Ca(V)2 and Ca(V)1 channels, and less so Ca(V)3 channels, it is unclear why there have not been major shifts toward dependence on other Ca(V) channels for synaptic transmission. Here, we provide a structural and functional profile of the Ca(V)2 channel cloned from the early-diverging animal Trichoplax adhaerens, which lacks a nervous system but possesses single gene homologues for Ca(V)1–Ca(V)3 channels. Remarkably, the highly divergent channel possesses similar features as human Ca(V)2.1 and other Ca(V)2 channels, including high voltage–activated currents that are larger in external Ba(2+) than in Ca(2+); voltage-dependent kinetics of activation, inactivation, and deactivation; and bimodal recovery from inactivation. Altogether, the functional profile of Trichoplax Ca(V)2 suggests that the core features of presynaptic Ca(V)2 channels were established early during animal evolution, after Ca(V)1 and Ca(V)2 channels emerged via proposed gene duplication from an ancestral Ca(V)1/2 type channel. The Trichoplax channel was relatively insensitive to mammalian Ca(V)2 channel blockers ω-agatoxin-IVA and ω-conotoxin-GVIA and to metal cation blockers Cd(2+) and Ni(2+). Also absent was the capacity for voltage-dependent G-protein inhibition by co-expressed Trichoplax Gβγ subunits, which nevertheless inhibited the human Ca(V)2.1 channel, suggesting that this modulatory capacity evolved via changes in channel sequence/structure, and not G proteins. Last, the Trichoplax channel was immunolocalized in cells that express an endomorphin-like peptide implicated in cell signaling and locomotive behavior and other likely secretory cells, suggesting contributions to regulated exocytosis.