Nicotinic Acetylcholine Receptors Are Novel Targets of APETx-like Toxins from the Sea Anemone <i>Heteractis magnifica</i>.

The nicotinic acetylcholine receptors (nAChRs) are prototypical ligand-gated ion channels, provide cholinergic signaling, and are modulated by various venom toxins and drugs in addition to neurotransmitters. Here, four APETx-like toxins, including two new toxins, named Hmg 1b-2 Met_ox and Hmg 1b-5, were isolated from the sea anemone <i>Heteractis magnifica</i> and characterized as novel nAChR ligands and acid-sensing ion channel (ASIC) modulators. All peptides competed with radiolabeled α-bungarotoxin for binding to <i>Torpedo californica</i> muscle-type and human α7 nAChRs. Hmg 1b-2 potentiated acetylcholine-elicited current in human α7 receptors expressed in <i>Xenopus laevis</i> oocytes. Moreover, the multigene family coding APETx-like peptides library from <i>H. magnifica</i> was described and in silico surface electrostatic potentials of novel peptides were analyzed. To explain the 100% identity of some peptide isoforms between <i>H. magnifica</i> and <i>H. crispa</i>, 18S rRNA, COI, and ITS analysis were performed. It has been shown that the sea anemones previously identified by morphology as <i>H. crispa</i> belong to the species <i>H. magnifica</i>.