title: TRPV3 is a calcium-permeable temperature-sensitive cation channel.
abstract: Transient receptor potential (TRP) proteins are cation-selective channels that function in processes as diverse as sensation and vasoregulation. Mammalian TRP channels that are gated by heat and capsaicin (>43 degrees C; TRPV1 (ref. 1)), noxious heat (>52 degrees C; TRPV2 (ref. 2)), and cooling (< 22 degrees C; TRPM8 (refs 3, 4)) have been cloned; however, little is known about the molecular determinants of temperature sensing in the range between approximately 22 degrees C and 40 degrees C. Here we have identified a member of the vanilloid channel family, human TRPV3 (hTRPV3) that is expressed in skin, tongue, dorsal root ganglion, trigeminal ganglion, spinal cord and brain. Increasing temperature from 22 degrees C to 40 degrees C in mammalian cells transfected with hTRPV3 elevated intracellular calcium by activating a nonselective cationic conductance. As in published recordings from sensory neurons, the current was steeply dependent on temperature, sensitized with repeated heating, and displayed a marked hysteresis on heating and cooling. On the basis of these properties, we propose that hTRPV3 is thermosensitive in the physiological range of temperatures between TRPM8 and TRPV1.
authors.affiliation: Howard Hughes Medical Institute, Children's Hospital, Harvard Medical School, Enders 1309, 320 Longwood Avenue, Boston, Massachusetts 02115, USA.
authors.forename: Haoxing
authors.initials: H
authors.lastname: Xu
authors.forename: I Scott
authors.initials: IS
authors.lastname: Ramsey
authors.forename: Suhas A
authors.initials: SA
authors.lastname: Kotecha
authors.forename: Magdalene M
authors.initials: MM
authors.lastname: Moran
authors.forename: Jayhong A
authors.initials: JA
authors.lastname: Chong
authors.forename: Deborah
authors.initials: D
authors.lastname: Lawson
authors.forename: Pei
authors.initials: P
authors.lastname: Ge
authors.forename: Jeremiah
authors.initials: J
authors.lastname: Lilly
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Silos-Santiago
authors.forename: Yu
authors.initials: Y
authors.lastname: Xie
authors.forename: Peter S
authors.initials: PS
authors.lastname: DiStefano
authors.forename: Rory
authors.initials: R
authors.lastname: Curtis
authors.forename: David E
authors.initials: DE
authors.lastname: Clapham
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D027682:Cation Transport Proteins; D002413:Cations, Divalent / Q000378:metabolism; D002463:Cell Membrane Permeability; D003001:Cloning, Molecular; D006224:Cricetinae; D004553:Electric Conductivity; D004594:Electrophysiology; D019143:Evolution, Molecular; D020869:Gene Expression Profiling; D006801:Humans; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D050916:TRPV Cation Channels; D013696:Temperature
chemical_list: D027682:Cation Transport Proteins; D002413:Cations, Divalent; D007473:Ion Channels; D012333:RNA, Messenger; D050916:TRPV Cation Channels; C459445:TRPV3 protein, human; D002118:Calcium