Polymodal nociceptors sense and integrate information on injurious mechanical, thermal, and chemical stimuli. Chemical signals either activate nociceptors or modulate their responses to other stimuli. One chemical known to activate or modulate responses of nociceptors is acetylcholine (ACh). Across evolution nociceptors express subunits of the nicotinic acetylcholine receptor (nAChR) family, a family of ACh-gated ion channels. The roles of ACh and nAChRs in nociceptor function are, however, poorly understood. Caenorhabditis elegans polymodal nociceptors, PVD, express nAChR subunits on their sensory arbor. Here we show that mutations reducing ACh synthesis and mutations in nAChR subunits lead to defects in PVD function and morphology. A likely cause for these defects is a reduction in cytosolic calcium measured in ACh and nAChR mutants. Indeed, overexpression of a calcium pump in PVD mimics defects in PVD function and morphology found in nAChR mutants. Our results demonstrate, for the first time, a central role for nAChRs and ACh in nociceptor function and suggest that calcium permeating via nAChRs facilitates activity of several signaling pathways within this neuron.
Bibliographical noteFunding Information:
We thank Yael Ben-David for the careful reading and helpful comments, Irini Topalidou for the lgc-12p ::GFP construct, Cody Smith for the pCJS01 construct, Wayne Davis and Erik Jorgensen for the Pcc::GFP-MCA3a construct. Some strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs ( P40 OD010440 ). This research project was supported in part by a grant from USAID's American Schools and Hospitals Abroad (ASHA) Program for the procurement of the confocal microscope LSM710. SJH is grateful to the Human Frontiers Science Program (HFSP) and the Research Fund Flanders (FWO). WSC and AG acknowledge the Deutsche Forschungsgemeinschaft (DFG) , grants FOR1279-P1 and EXC115 .
- Caenorhabditis elegans
- Nicotinic acetylcholine receptors
- Polymodal nociceptors