Received for publication December 15, 2006.
Revised February 7, 2007.
Accepted for publication February 21, 2007.

Activation of Single Nicotinic Receptor Channels from Caenorhabditis elegans Muscle

Abstract

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 non-mammalian model for the study of the nervous system as well as a model of parasitic nematodes. Nematode muscle nAChRs are of considerable interest as 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 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.

Key words: Nicotinic cholinergic, Single channel kinetics

This article has been cited by other articles:

				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. [Abstract] [Full Text] [PDF]