A Novel and Functionally Diverse Class of Acetylcholine-gated Ion Channels

Abstract:

Fast cholinergic neurotransmission is mediated by acetylcholine-gated ion channels; in particular, excitatory nicotinic acetylcholine receptors play well established roles in virtually all nervous systems. Acetylcholine-gated inhibitory channels have also been identified in some invertebrate phyla, yet their roles in the nervous system are less well understood. We report the existence of multiple new inhibitory acetylcholine-gated ion channels with diverse ligand binding properties in C. elegans . We identify three channels, LGC-40, LGC-57 and LGC-58, whose primary ligand is choline rather than acetylcholine, as well as the first evidence of a truly polymodal channel, LGC-39, which is activated by both cholinergic and aminergic ligands. Using our newly deorphanised channel evidence we uncover the surprising extent to which a single neuron expresses both excitatory and inhibitory channels, not only for acetylcholine but also the other major neurotransmitters. The results presented in this study offer a new insight into the potential evolutionary benefit of a vast and diverse repertoire of LGICs to generate complexity in an anatomically compact nervous system.