TRPs in mechanosensing and volume regulation.

Mechanosensitive channels allow cells to respond to changes in membrane stretch that occur due to external stimuli like pressure or flow or that occur because of osmotically induced cell swelling or shrinkage. Ion fluxes through the channels change the membrane potential and ion concentrations and link the stretch to cellular signalling. Changes in cellular activity evoked by mechanical stimuli can be used to elicit local tissue responses or can be transmitted further to generate more widespread responses. Channels can respond directly to membrane stress, can be conferred mechanosensitive by interaction with structural proteins, or can be activated by mechanosensitive signalling pathways. Because mechanosensitive channels are often nonselective cation channels, and invertebrate TRP isoforms are involved in mechanosensation, many of the mammalian TRP isoforms have been investigated with regard to their mechanosensitivity. There is evidence that members of the TRPC, TRPV, TRPM, TRPA and TRPP subfamilies could be in some way mechanosensitive, and each of the activation mechanisms described above is used by a TRP channel. TRP channels may be involved in mechanosensitive processes ranging from flow and pressure sensing in the vasculature and other organs to mechanosensation in sensory neurones and sensory organs. There is also evidence for a role of mechano- or osmosensitive TRP isoforms in osmosensing and the regulation of cell volume. Often, a number of different TRP isoforms have been implicated in a single type of mechanosensitive response. In many cases, the involvement of the isoforms needs to be confirmed, and their exact role in the signalling process determined.