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

Fast cholinergic neurotransmission is mediated by acetylcholine-gated ion channels; in particular, excitatory nicotinic acetyl- choline 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 exis- tence of multiple new inhibitory ion channels with diverse ligand activation properties in Caenorhabditis 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 new ligand-receptor pairs we uncover the surprising extent to which single neurons in the hermaphrodite nervous system express both excitatory and inhibitory channels, not only for acetylcholine but also for the other major neurotransmitters. The results presented in this study offer new insight into the potential evolutionary benefit of a vast and diverse repertoire of ligand- gated ion channels to generate complexity in an anatomically compact nervous system.

Automated summary

This study identifies multiple new inhibitory ion channels with diverse ligand activation properties in Caenorhabditis elegans. These channels have inhibitory effects on acetylcholine and also show both excitatory and inhibitory effects on other major neurotransmitters. The findings shed light on the important role of diverse ligand-gated ion channels in generating complexity in a compact anatomical nervous system.