C. elegans has a family of four putative ion channel subunits that are closely related to the C. elegans
osm-9 gene.
osm-9 encodes a putative ion channel with homology to the vertebrate capsaicin receptor, a cation channel expressed in pain-sensing neurons and gated by the active component of chili peppers. In the amphid neuron AWA, OSM-9 localizes to sensory cilia, suggesting a direct role in sensory transduction.
osm-9 mutants are defective in a wide range of sensory functions in C. elegans including chemosensation, mechanosensation, osmosensation, and certain forms of olfactory adaptation. Four relatives of
osm-9 are each expressed in subsets of
osm-9 -expressing cells. We call these genes ocr (
osm-9 /capsaicin receptor-related) genes and have generated mutations in two of them. Based on GFP fusions,
ocr-1 is expressed primarily in AWA,
ocr-2 is expressed in AWA, ASH, ADL, ADF, PHA, and PHB,
ocr-3 is expressed in rectal gland cells, and
ocr-4 is expressed in OLQ mechanosensory neurons. All ocr genes are expressed in subsets of
osm-9 -expressing cells. We hypothesized that the OCR channels might coassemble with OSM-9 to form heteromultimeric complexes. Like OSM-9, OCR-2 localizes to sensory cilia. Proper localization of OCR-2 requires
osm-9 , suggesting that these proteins may indeed associate. We propose that different combinations of subunits may account for the distinct functions of
osm-9 in different sensory neurons. Mutations in
ocr-2 recapitulate a subset of
osm-9 ''s defects: there are dramatic defects in AWA-mediated chemotaxis and ASH-mediated avoidance behaviors. By contrast,
ocr-1 mutants do not have obvious sensory defects. However, both
ocr-1 and
ocr-2 appear to contribute to activity-dependent gene regulation in AWA (A. Kahn and C.I.B.), so both proteins are probably functional. Although heterologous expression of VR1 does not rescue ocr behavioral phenotypes in C.elegans , mammalian VR1 is functional and responsive to capsaicin in the C. elegans nociceptive neuron ASH. We have used this observation as the basis for a method of reversible, drug-inducible activation of sensory neurons in C. elegans . Animals expressing VR1 in ASH reverse in response to capsaicin. Capsaicin bypassed several ASH molecules normally required for signaling, suggesting that the channel depolarizes the neurons directly. The effect of VR1 in ASH required the endogenous vesicular glutamate transporter EAT-4. The introduction of a channel with a novel pharmacology into sensory neurons may have general utility for answering temporal questions about neuronal activity.