Physiological significances of TRP–ANO1 interaction

A calcium–activated chloride channel, anoctamin 1 (ANO1), is strongly activated by intracellular calcium increases through activation of transient receptor potential (TRP) channel because these ion channels physically interact with one another on the plasma membrane. The functional inter action occurs when TRP channels and ANO1 are within 20 nm, although ANO1 could be activated by global calcium increases as well. Recently, we obtained data that suggested the significance of the inter actions in the choroid plexus and primary sensory neurons. TRPV4 and ANO1 inter action in the apical membrane of choroid plexus epithelial cells could induce water efflux to the ventricle side. This interaction could be important in the homeostatic release of cerebro spinal fluid. That is, TRPV4 could be activated by the combined effects of body temperature and membrane stretch evoked by continuous water influx from the basolateral (capillary) side. Furthermore, TRPV1 and ANO1 inter action enhances TRPV1–mediated pain sensation. TRPV1 and ANO1 are co–expressed in small dorsal root ganglion (DRG) neurons. In our study, ANO1 current was induced by capsaicin application in small DRG neurons. ANO1–dependent depolarization following TRPV1 activation evoked action potentials. Furthermore, capsaicin–evoked pain–related behaviors in mice were strongly inhibited by a selective ANO1 blocker whereas the compound did not completely abolish the behaviors. The significance of these observations is that selective ANO1 inhibi tion reduces pain sensation. We also investigated non–specific inhibitory effects of chemicals on ion channel activities. We recently found that 4–isopropylcyclohexanol (4–iPr–CyH–OH) has an analgesic effect on burning pain sensation. 4–iPr–CyH–OH, a menthol analogue, is an aliphatic higher alcohol and used as a food– or flavor–additive. This compound inhibits TRPV1 and ANO1 without agonistic effects on TRPV1, TRPA1 or ANO1. Menthol also inhibits TRPV1 and ANO1, however, the TRPM8 agonist activates TRPA1 followed by pain sensation. Therefore, 4–iPr–CyH–OH might be a novel analgesia, Symposium 3 : The 39th Annual Meeting of JASP