title: 2-aminoethoxydiphenyl borate activates and sensitizes the heat-gated ion channel TRPV3.
abstract: Six of the mammalian transient receptor potential (TRP) ion channel subtypes are nonselective cation channels that can be activated by increases or decreases in ambient temperature. Five of them can alternatively be activated by nonthermal stimuli such as capsaicin [transient receptor potential vanilloid 1 (TRPV1)] or hypo-osmolarity (TRPV2 and TRPV4). No nonthermal stimuli have yet been described for TRPV3, a warmth-gated ion channel expressed prominently in skin keratinocytes. Here, we demonstrate that 2-aminoethoxydiphenyl borate (2-APB), a compound used to inhibit store-operated Ca2+ channels and IP3 receptors, produces robust activation of recombinant TRPV3 in human embryonic kidney 293 cells with an EC50 of 28 microm. 2-APB also sensitizes TRPV3 to activation by heat, even at subthreshold concentrations. In inside-out membrane patches from TRPV3-expressing cells, 2-APB increases the open probability of TRPV3. Also, whereas heat alone is capable of activating TRPV3-mediated currents in only a small proportion of primary mouse keratinocytes, 2-APB activates heat-evoked, TRPV3-mediated currents in the majority of these cells. Together, these findings identify 2-APB as the first known chemical activator of TRPV3 and enhance the notion that TRPV3 participates in the detection of heat by keratinocytes.
authors.affiliation: Department of Biological Chemistry, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Man-Kyo
authors.initials: MK
authors.lastname: Chung
authors.forename: Hyosang
authors.initials: H
authors.lastname: Lee
authors.forename: Atsuko
authors.initials: A
authors.lastname: Mizuno
authors.forename: Makoto
authors.initials: M
authors.lastname: Suzuki
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Caterina
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000494:pharmacology*; D027682:Cation Transport Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006358:Hot Temperature; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects* / Q000502:physiology; D007473:Ion Channels / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018408:Patch-Clamp Techniques; D011994:Recombinant Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D050916:TRPV Cation Channels; D013697:Thermosensing / Q000502:physiology; D014162:Transfection
chemical_list: D001896:Boron Compounds; D027682:Cation Transport Proteins; D007473:Ion Channels; D011994:Recombinant Proteins; D050916:TRPV Cation Channels; C459445:TRPV3 protein, human; C416986:TRPV4 protein, human; C486760:Trpv3 protein, mouse; C486576:Trpv4 protein, mouse; C109986:2-aminoethoxydiphenyl borate