RT Journal Article
SR Electronic
T1 Activation of TRPV1 channels inhibits mechanosensitive Piezo channel activity by depleting membrane phosphoinositides
JF Science Signaling
JO Sci. Signal.
FD American Association for the Advancement of Science
SP ra15
OP ra15
DO 10.1126/scisignal.2005667
VO 8
IS 363
A1 Borbiro, Istvan
A1 Badheka, Doreen
A1 Rohacs, Tibor
YR 2015
UL http://stke.sciencemag.org/content/8/363/ra15.abstract
AB Ion channels are essential to mediating the sensation of pain and pressure. The chemical in chilis that makes them hot is capsaicin, which activates the calcium-permeable channel TRPV1, and this chemical is also used as a topical analgesic. Borbiro et al. found that capsaicin activation of TRPV1 inhibited the mechanosensitive Piezo channels by depleting specific phosphoinositides in the plasma membrane. These results may explain some of the analgesic effects of this chemical.Capsaicin is an activator of the heat-sensitive TRPV1 (transient receptor potential vanilloid 1) ion channels and has been used as a local analgesic. We found that activation of TRPV1 channels with capsaicin either in dorsal root ganglion neurons or in a heterologous expression system inhibited the mechanosensitive Piezo1 and Piezo2 channels by depleting phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and its precursor phosphatidylinositol 4-phosphate [PI(4)P] from the plasma membrane through Ca2+-induced phospholipase Cδ (PLCδ) activation. Experiments with chemically inducible phosphoinositide phosphatases and receptor-induced activation of PLCβ indicated that inhibition of Piezo channels required depletion of both PI(4)P and PI(4,5)P2. The mechanically activated current amplitudes decreased substantially in the excised inside-out configuration, where the membrane patch containing Piezo1 channels is removed from the cell. PI(4,5)P2 and PI(4)P applied to these excised patches inhibited this decrease. Thus, we concluded that Piezo channel activity requires the presence of phosphoinositides, and the combined depletion of PI(4,5)P2 and PI(4)P reduces channel activity. In addition to revealing a role for distinct membrane lipids in mechanosensitive ion channel regulation, these data suggest that inhibition of Piezo2 channels may contribute to the analgesic effect of capsaicin.