TRP channels in mechanosensation: direct or indirect activation?

Key Points Although many ion channels are implicated in mechanosensation, it is hard to be sure that such channels are directly gated by mechanical force. Criteria that help to establish direct gating include specific tests such as: does mechanosensation involve direct activation of a channel? does the candidate protein participate in mechanical transduction? is the candidate protein mechanically sensitive? is the candidate protein a pore-forming subunit? and is the candidate protein a force-sensing subunit? Various transient receptor potential (TRP) channels are involved in mechanosensation in non-neural cells — including TRPC1 in oocytes, TRPC3 and TRPC6 in myogenic tone, TRPV1 in bladder, PKD1 and PKD2 in flow-sensing in kidney and TRPV4 in osmosensing. It is difficult to establish direct gating for most of these, partly because the stimuli are slow; evidence suggests that many of them are activated by second messengers. Forward genetics has revealed a role for TRP channels in Caenorhabditis elegans mechanosensation, specifically, for the worm homologues of PKD1 and PKD2 in male sensation of vulva location and for OSM-9 and OCR-2 in nose touch and osmosensation. Remarkably, the vertebrate TRPV4 can rescue mutations in the worm OSM-9, when expressed in worm sensory neurons. The ability of Drosophila melanogaster to respond to painful heat and touch stimuli involves painless, a TRP channel expressed in multidendritic neurons, and TRPN1, a bristle deflection sensor. Bristle deflection almost certainly involves a directly gated channel, which may be TRPN1 itself. Three TRP channels (TRPN1, Nanchung and Inactive) are required for proper hearing in Drosophila , a process that involves mechanosensation of the sound-evoked rotation of the antenna, but it is not clear which is the direct sensor and which have the necessary supporting roles. A variety of TRP channels that sense sound and head movements are expressed by hair cells of the vertebrate inner ear; these include TRPV4, TRPML3 and TRPA1. There is some evidence that supports a role for each of them in mechanosensation, but there is more evidence that casts doubt on a direct involvement. At present there is no good candidate for the hair-cell transduction channel. The short latency of the receptor current in vertebrate touch and proprioceptive neurons suggests direct gating of a still unidentified mechanosensory channel. One TRP channel, TRPA1, is involved in sensing painful mechanical stimuli but it may b