Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Sci Signal
2015 Feb 10;8363:ra15. doi: 10.1126/scisignal.2005667.
Show Gene links
Show Anatomy links
Activation of TRPV1 channels inhibits mechanosensitive Piezo channel activity by depleting membrane phosphoinositides.
Borbiro I
,
Badheka D
,
Rohacs T
.
???displayArticle.abstract???
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 Ca(2+)-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.
???displayArticle.pubmedLink???
25670203
???displayArticle.pmcLink???PMC4527171 ???displayArticle.link???Sci Signal ???displayArticle.grants???[+]
Albuisson,
Dehydrated hereditary stomatocytosis linked to gain-of-function mutations in mechanically activated PIEZO1 ion channels.
2013, Pubmed
Albuisson,
Dehydrated hereditary stomatocytosis linked to gain-of-function mutations in mechanically activated PIEZO1 ion channels.
2013,
Pubmed
Altier,
Spicing up the sensation of stretch: TRPV1 controls mechanosensitive Piezo channels.
2015,
Pubmed
Bae,
The mechanosensitive ion channel Piezo1 is inhibited by the peptide GsMTx4.
2011,
Pubmed
Bae,
Xerocytosis is caused by mutations that alter the kinetics of the mechanosensitive channel PIEZO1.
2013,
Pubmed
Bae,
Human PIEZO1: removing inactivation.
2013,
Pubmed
Balla,
Maintenance of hormone-sensitive phosphoinositide pools in the plasma membrane requires phosphatidylinositol 4-kinase IIIalpha.
2008,
Pubmed
Balla,
Phosphoinositides: tiny lipids with giant impact on cell regulation.
2013,
Pubmed
Besch,
High-speed pressure clamp.
2002,
Pubmed
Brenneis,
Phenotyping the function of TRPV1-expressing sensory neurons by targeted axonal silencing.
2013,
Pubmed
Cavanaugh,
Trpv1 reporter mice reveal highly restricted brain distribution and functional expression in arteriolar smooth muscle cells.
2011,
Pubmed
Coste,
Gain-of-function mutations in the mechanically activated ion channel PIEZO2 cause a subtype of Distal Arthrogryposis.
2013,
Pubmed
Coste,
Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels.
2010,
Pubmed
Coste,
Piezo proteins are pore-forming subunits of mechanically activated channels.
2012,
Pubmed
Delmas,
Mechano-gated ion channels in sensory systems.
2013,
Pubmed
Drew,
Distinct mechanosensitive properties of capsaicin-sensitive and -insensitive sensory neurons.
2002,
Pubmed
Dubin,
Inflammatory signals enhance piezo2-mediated mechanosensitive currents.
2012,
Pubmed
Eijkelkamp,
A role for Piezo2 in EPAC1-dependent mechanical allodynia.
2013,
Pubmed
Fruman,
Phosphoinositide kinases.
1998,
Pubmed
Gottlieb,
Gating the mechanical channel Piezo1: a comparison between whole-cell and patch recording.
2012,
Pubmed
Gottlieb,
Piezo1: properties of a cation selective mechanical channel.
2012,
Pubmed
Hamill,
Induced membrane hypo/hyper-mechanosensitivity: a limitation of patch-clamp recording.
1997,
Pubmed
Hammond,
PI4P and PI(4,5)P2 are essential but independent lipid determinants of membrane identity.
2012,
Pubmed
Hilgemann,
Regulation of cardiac Na+,Ca2+ exchange and KATP potassium channels by PIP2.
1996,
Pubmed
Hirono,
Hair cells require phosphatidylinositol 4,5-bisphosphate for mechanical transduction and adaptation.
2004,
Pubmed
Karashima,
Modulation of the transient receptor potential channel TRPA1 by phosphatidylinositol 4,5-biphosphate manipulators.
2008,
Pubmed
Kim,
Local application of capsaicin alleviates mechanical hyperalgesia after spinal nerve transection.
2008,
Pubmed
Kim,
The role of Drosophila Piezo in mechanical nociception.
2012,
Pubmed
Kruse,
Muscarinic acetylcholine receptors: novel opportunities for drug development.
2014,
Pubmed
Lukacs,
Distinctive changes in plasma membrane phosphoinositides underlie differential regulation of TRPV1 in nociceptive neurons.
2013,
Pubmed
,
Xenbase
Lukacs,
Dual regulation of TRPV1 by phosphoinositides.
2007,
Pubmed
,
Xenbase
Lukacs,
Promiscuous activation of transient receptor potential vanilloid 1 (TRPV1) channels by negatively charged intracellular lipids: the key role of endogenous phosphoinositides in maintaining channel activity.
2013,
Pubmed
,
Xenbase
Maksimovic,
Epidermal Merkel cells are mechanosensory cells that tune mammalian touch receptors.
2014,
Pubmed
Mishra,
TRPV1-lineage neurons are required for thermal sensation.
2011,
Pubmed
Nilius,
Pressing and squeezing with Piezos.
2010,
Pubmed
Pospisilova,
Post-operative pain behavior in rats is reduced after single high-concentration capsaicin application.
2006,
Pubmed
Quinn,
Monitoring changes in membrane phosphatidylinositol 4,5-bisphosphate in living cells using a domain from the transcription factor tubby.
2008,
Pubmed
Ranade,
Piezo2 is the major transducer of mechanical forces for touch sensation in mice.
2014,
Pubmed
Ranade,
Piezo1, a mechanically activated ion channel, is required for vascular development in mice.
2014,
Pubmed
Rebecchi,
Structure, function, and control of phosphoinositide-specific phospholipase C.
2000,
Pubmed
Rohacs,
Regulation of transient receptor potential channels by the phospholipase C pathway.
2013,
Pubmed
Rohacs,
Recording macroscopic currents in large patches from Xenopus oocytes.
2013,
Pubmed
,
Xenbase
Rohács,
PI(4,5)P2 regulates the activation and desensitization of TRPM8 channels through the TRP domain.
2005,
Pubmed
Rugiero,
Kinetic properties of mechanically activated currents in spinal sensory neurons.
2010,
Pubmed
Saarikangas,
Regulation of the actin cytoskeleton-plasma membrane interplay by phosphoinositides.
2010,
Pubmed
Sachs,
Stretch-activated ion channels: what are they?
2010,
Pubmed
Samways,
Tunable calcium current through TRPV1 receptor channels.
2008,
Pubmed
Santagata,
G-protein signaling through tubby proteins.
2001,
Pubmed
Srinivas,
Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus.
2001,
Pubmed
Suchyna,
Biophysics and structure of the patch and the gigaseal.
2009,
Pubmed
Suh,
PIP2 is a necessary cofactor for ion channel function: how and why?
2008,
Pubmed
Suh,
Recovery from muscarinic modulation of M current channels requires phosphatidylinositol 4,5-bisphosphate synthesis.
2002,
Pubmed
Sui,
Activation of the atrial KACh channel by the betagamma subunits of G proteins or intracellular Na+ ions depends on the presence of phosphatidylinositol phosphates.
1998,
Pubmed
,
Xenbase
Szallasi,
Vanilloid (Capsaicin) receptors and mechanisms.
1999,
Pubmed
van der Wal,
Monitoring agonist-induced phospholipase C activation in live cells by fluorescence resonance energy transfer.
2001,
Pubmed
Woo,
Piezo2 is required for Merkel-cell mechanotransduction.
2014,
Pubmed
Xu,
Kinetic analysis of receptor-activated phosphoinositide turnover.
2003,
Pubmed
Yudin,
Decrease in phosphatidylinositol 4,5-bisphosphate levels mediates desensitization of the cold sensor TRPM8 channels.
2011,
Pubmed
Zakharian,
Gating of transient receptor potential melastatin 8 (TRPM8) channels activated by cold and chemical agonists in planar lipid bilayers.
2010,
Pubmed
Zakharian,
Intracellular ATP supports TRPV6 activity via lipid kinases and the generation of PtdIns(4,5) P₂.
2011,
Pubmed
,
Xenbase
Zarychanski,
Mutations in the mechanotransduction protein PIEZO1 are associated with hereditary xerocytosis.
2012,
Pubmed
