Functional Control of Cold- and Menthol-Sensitive TRPM8 Ion Channels by Phosphatidylinositol 4,5-Bisphosphate

• DOI: 10.1523/jneurosci.3632-04.2005
• Publication Date: 2005-02-16T20:58:29Z
• Authors: Beiying Liu; Feng Qin
• Keywords: TRPM8; Phosphatidylinositol 4,5-bisphosphate; Transduction (biophysics)

Cold is detected by a small subpopulation of peripheral thermoreceptors. TRPM8, cloned menthol- and cold-sensitive ion channel, has been suggested to mediate cold transduction in the innocuous range. The channel shows robust response whole-cell recordings but exhibits markedly reduced activity excised membrane patches. Here we report that phosphatidylinositol 4,5-bisphosphate (PIP 2 ) an essential regulator function. rundown prevented lipid phosphatase inhibitors. Application exogenous PIP both activates directly restores activity. Whole-cell experiments involving intracellular dialysis with polyvalent cations, inhibition synthesis kinases, receptor-mediated hydrolysis show also modulates intact cells. crucial role on function TRPM8 suggests level may be important vivo . opposite effects vanilloid receptor TRPV1 implies have dual actions as bimodal switch selectively control heat- cold-induced responses nociceptors expressing channels.