TMC-1 Mediates Alkaline Sensation in C. elegans through Nociceptive Neurons

Noxious pH triggers pungent taste and nocifensive behavior. While the mechanisms underlying acidic pH sensation have been extensively characterized, little is known about how animals sense alkaline pH in the environment. TMC genes encode a family of evolutionarily conserved membrane proteins whose functions are largely unknown. Here, we characterize C. elegans TMC-1, which was suggested to form a Na(+)-sensitive channel mediating salt chemosensation. Interestingly, we find that TMC-1 is required for worms to avoid noxious alkaline environment. Alkaline pH evokes an inward current in nociceptive neurons, which is primarily mediated by TMC-1 and to a lesser extent by the TRP channel OSM-9. However, unlike OSM-9, which is sensitive to both acidic and alkaline pH, TMC-1 is only required for alkali-activated current, revealing a specificity for alkaline sensation. Ectopic expression of TMC-1 confers alkaline sensitivity to alkali-insensitive cells. Our results identify an unexpected role for TMCs in alkaline sensation and nociception.