Abstract
The genome of the nematode Caenorhabditis elegans encodes a surprisingly large and diverse superfamily of genes encoding Cys loop ligand-gated ion channels. Here we report the first cloning, expression, and pharmacological characterization of members of a family of anion-selective acetylcholine receptor subunits. Two subunits, ACC-1 and ACC-2, form homomeric channels for which acetylcholine and arecoline, but not nicotine, are efficient agonists. These channels are blocked by d-tubocurarine but not by alpha-bungarotoxin. We provide evidence that two additional subunits, ACC-3 and ACC-4, interact with ACC-1 and ACC-2. The acetylcholine-binding domain of these channels appears to have diverged substantially from the acetylcholine-binding domain of nicotinic receptors.
Highlights
Fast cholinergic neurotransmission is generally mediated by nicotinic acetylcholine (ACh)1 receptors
We have identified a new family of Cys loop ligand-gated ion channel (LGIC), the nematode ACh-gated chloride channels
We report the first molecular characterization of an anion-selective ACh receptor and show that a distinct class of Cys loop LGICs has evolved to mediate inhibitory cholinergic neurotransmission
Summary
Fast (ionotropic) cholinergic neurotransmission is generally mediated by nicotinic acetylcholine (ACh)1 receptors (nAChRs). The ACh-gated chloride channels in Aplysia neurons respond to several agonists and antagonists of nAChRs, indicating that, like the nAChRs, they may belong to the superfamily of Cys loop ligand-gated ion channel (LGIC) subunits. Subunits of the Cys loop LGIC superfamily share a topology that consists of a large extracellular ligand-binding domain and four transmembrane domains that form the ion-selective pore (4 – 6).
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