Activated L-Type Calcium Channels Inhibit Chemosensitized Nematocyst Discharge from Sea Anemone Tentacles

Because in vivo nematocyst discharge requires extracellular Ca²⁺, Ca²⁺ channels have been suspected to be involved; but their identity and role have not been revealed. The majority of nematocysts that discharge from sea anemone tentacles are under the control of sensitizing chemoreceptors for N-acetylated sugars (e.g., N-acetylneuraminic acid). Activated chemoreceptors predispose contact-sensitive mechanoreceptors to trigger discharge. We show that activating L-type Ca²⁺ channels inhibits N-acetylneuraminic acid-sensitized discharge, contrary to a previous suggestion. In addition, inhibiting L-type channels increases sensitivity to N-acetylneuraminic acid. Specifically, we show that the L-type Ca²⁺ channel activator (-)-Bay K 8644 dose-dependently inhibits N-acetylneuraminic acid-sensitized discharge, as does raising ambient Ca²⁺ levels. We also show that lowering extracellular Ca²⁺ levels or adding any of several selective and chemically distinct L-type Ca²⁺ channel blockers, including dihydropyridines, dose-dependently increases N-acetylneuraminic acid sensitivity and broadens the dynamic range of N-acetylneuraminic acid sensitization. Consistent with these functional findings, Aiptasia pallida expresses an L-type Ca²⁺ channel α subunit transcript that encodes a conserved dihydropyridine-binding site. Phylogenetic analysis confirms a close relationship of the Aiptasia Ca²⁺ channel α subunit sequence between anemones, anthozoans, and cnidarians that extends into protostomal and deuterostomal bilaterians. We conclude that L-type Ca²⁺ channel activity modulates N-acetylneuraminic acid-sensitized nematocyst discharge in a push-pull manner depending on channel activity state. Our findings suggest that L-type channel activation promotes chemosensory desensitization, and we predict that N-acetylneuraminic acid chemoreceptor signaling will activate L-type channels.