Activation of Single Nicotinic Receptor Channels from Caenorhabditis elegans Muscle

• DOI: 10.1124/mol.106.033514
• Publication Date: 2007-02-22T01:56:26Z
• Authors: Diego Rayes; Marina Flamini; Guillermina Hernando; Cecilia Bouzat
• Keywords: 0301 basic medicine; Muscles; Receptors, Nicotinic; Acetylcholine; 3. Good health; 03 medical and health sciences; Levamisole; https://purl.org/becyt/ford/1.6; Morantel; Animals; Mutant Proteins; Pyrantel; https://purl.org/becyt/ford/1; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Ion Channel Gating

Nicotinic acetylcholine receptors (nAChRs) are pentameric neurotransmitter-gated ion channels that mediate synaptic transmission throughout the nervous system in vertebrates and invertebrates. Caenorhabditis elegans is a nonmammalian model for the study of the nervous system and a model of parasitic nematodes. Nematode muscle nAChRs are of considerable interest because they are targets for anthelmintic drugs. We show single-channel activity of C. elegans muscle nAChRs for the first time. Our results reveal that in the L1 larval stage acetylcholine (ACh) activates mainly a levamisole-sensitive nAChR (L-AChR). A single population of 39 pS channels, which are 5-fold more sensitive to levamisole than ACh, is detected. In contrast to mammalian nAChRs, open durations are longer for levamisole than for ACh. Studies in mutant strains reveal that UNC-38, UNC-63, and UNC-29 subunits are assembled into a single L-AChR in the L1 stage and that these subunits are irreplaceable, suggesting that they are vital for receptor function throughout development. Recordings from a strain mutated in the LEV-1 subunit show a main population of channels with lower conductance (26 pS), prolonged open durations, and reduced sensitivity to levamisole. Thus, although LEV-1 is preferentially incorporated into native L-AChRs, receptors lacking this subunit can still function. No single-channel activity from levamisole-insensitive nAChRs is detected. Thus, during neuromuscular transmission in C. elegans, the majority of ACh-activated current flows through L-AChRs. This study contributes to the understanding of the molecular mechanisms underlying functional diversity of the nAChR family and offers an excellent strategy to test novel antiparasitic drugs.