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The Caenorhabditis elegans lev‐8 gene encodes a novel type of nicotinic acetylcholine receptor α subunit

We have cloned Caenorhabditis elegans lev‐8 and demonstrated that it encodes a novel nicotinic acetylcholine receptor (nAChR) subunit (previously designated ACR‐13), which has functional roles in body wall and uterine muscles as part of a levamisole‐sensitive receptor. LEV‐8 is an α subunit and is the first to be described from the ACR‐8‐like group, a new class of nAChR with atypical acetylcholine‐binding site (loop C) and channel‐lining motifs. A single base pair change in the first intron of lev‐8 in lev‐8(x15) mutants leads to alternative splicing and the introduction of a premature stop codon. lev‐8(x15) worms are partially resistant to levamisole‐induced egg laying and paralysis, phenotypes rescued by expression of the wild‐type gene. lev‐8(x15) worms also show reduced rates of pharyngeal pumping. Electrophysiological recordings from body wall muscle show that currents recorded in response to levamisole have reduced amplitude in lev‐8(x15) compared with wild‐type animals. Consistent with these phenotypic observations, green fluorescent protein fused to LEV‐8 is expressed in body wall and uterine muscle, motor neurons and epithelial‐derived socket cells. Thus, LEV‐8 is a levamisole receptor subunit and exhibits the most diverse expression pattern of any invertebrate nAChR subunit studied to date.