No abstract

The role of T-type calcium channels in animals without nervous systems is unknown. Smith et al. characterize TCav3 from Trichoplax adhaerens, finding expression in neurosecretory-like cells and preference for Ca2+ over Na+ via strong extracellular Ca2+ block, despite low selectivity for Ca2+ in the pore.

The dominant role of CaV2 voltage-gated calcium channels for driving neurotransmitter release is broadly conserved. Given the overlapping functional properties of CaV2 and CaV1 channels, and less so CaV3 channels, it is unclear why there have not been major shifts towards dependency on other CaV channels for synaptic transmission. Here, we provide a structural and functional profile of the CaV2 channel cloned from the early-diverging animal Trichoplax adhaerens, which lacks a nervous system but possess single gene homologues for CaV1-CaV3 channels. Remarkably, the highly divergent channel possesses similar features as human CaV2.1 and other CaV2 channels, including high voltage-activated currents that are larger in external Ba2+ than Ca2+, voltage dependent kinetics of activation, inactivation and deactivation, and bimodal recovery from inactivation. Altogether, the functional profile of Trichoplax CaV2 suggests that the core features of pre-synaptic CaV2 channels were established early during animal evolution, after CaV1 and CaV2 channels emerged via proposed gene duplication from an ancestral CaV1/2 type channel. The Trichoplax channel was relatively insensitive to mammalian CaV2 channel blockers ω-agatoxin-IVA and ω-conotoxin-GVIA, and to metal cation blockers Cd2+ and Ni2+. Also absent was the capacity for voltage-dependent G-protein inhibition by co-expressed Trichoplax Gβγ subunits, which nevertheless inhibited the human CaV2.1 channel suggesting that this modulatory capacity evolved via changes in channel sequence/structure, and not G-proteins. Lastly, 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.

No abstract

No abstract