A Novel and Functionally Diverse Class of Acetylcholine-gated Ion Channels
Fast cholinergic neurotransmission is mediated by pentameric acetylcholine-gated ion channels; in particular, cationic nicotinic acetylcholine receptors play well-established roles in virtually all nervous systems. Acetylcholine-gated anion channels have also been identified in some invertebrate phyla, yet their roles in the nervous system are less well-understood. Here we describe the functional properties of five previously-uncharacterized acetylcholine-gated anion channels from C. elegans, including four from a novel nematode specific subfamily known as the diverse group. In addition to their activation by acetylcholine, these diverse group channels are activated at physiological concentrations by other ligands; three, encoded by the lgc-40, lgc-57 and lgc-58 genes, are activated by choline, while lgc-39 encoded channels are activated by octopamine and tyramine. Intriguingly, these and other acetylcholine-gated anion channels show extensive co-expression with cation-selective nicotinic receptors, implying that many cholinergic synapses may have both excitatory and inhibitory potential. Thus, the evolutionary expansion of cholinergic ligand-gated ion channels may enable complex synaptic signalling in an anatomically compact nervous system.