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First published on February 21, 2007; DOI: 10.1124/mol.106.033514

0026-895X/07/7105-1407-1415$20.00
Mol Pharmacol 71:1407-1415, 2007

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Activation of Single Nicotinic Receptor Channels from Caenorhabditis elegans Muscle

Diego Rayes, Marina Flamini, Guillermina Hernando, and Cecilia Bouzat

Instituto de Investigaciones Bioquímicas, Universidad Nacional del Sur-CONICET, Bahía Blanca, Argentina

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.

Received December 14, 2006; accepted February 21, 2007

Address correspondence to: Dr. Cecilia Bouzat, Instituto de Investigaciones Bioquímicas, Camino La Carrindanga Km 7, B8000FWB, Bahía Blanca, Argentina. E-mail: inbouzat{at}criba.edu.ar




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H. Qian, A. P. Robertson, J. A. Powell-Coffman, and R. J. Martin
Levamisole resistance resolved at the single-channel level in Caenorhabditis elegans
FASEB J, September 1, 2008; 22(9): 3247 - 3254.
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