Journal Club 2014-03-28

TRPV3 is a calcium-permeable temperature-sensitive cation channel

12077604-Nature-2002-TRPV3 is a calcium-permeable temperature-sensitive

Haoxing Xu*†, I. Scott Ramsey*†, Suhas A. Kotecha*†,
Magdalene M. Moran‡, Jayhong A. Chong*, Deborah Lawson§, Pei Ge§, Jeremiah Lilly§, Inmaculada Silos-Santiago§, Yu Xie§,
Peter S. DiStefano§k, Rory Curtis§k & David E. Clapham*

* Howard Hughes Medical Institute, Children’s Hospital, Harvard Medical School, Enders 1309, 320 Longwood Avenue, Boston, Massachusetts 02115, USA ‡ Program in Neuroscience, Harvard Medical School, Goldenson Building B2-228, 220 Longwood Avenue, Boston, Massachusetts 02115, USA
§ Millennium Pharmaceuticals Inc., 75 Sidney Street, Cambridge, Massachusetts 02139, USA
† These authors contributed equally to this work

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 8C; TRPV1 (ref. 1)), noxious heat (>52 8C; TRPV2 (ref. 2)), and cooling (< 22 8C; TRPM8 (refs 3, 4)) have been cloned; however, little is known about the molecular determinants of temperature sensing in the range between ,22 8C and 40 8C. 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 228C to 408C in mammalian cells transfected with hTRPV3 elevated intracellular calcium by activating a nonselective cat- ionic conductance. As in published recordings from sensory neurons, the current was steeply dependent on temperature, sensitized with repeated heating, and displayed a marked hyster- esis on heating and cooling5–10. On the basis of these properties, we propose that hTRPV3 is thermosensitive in the physiological range of temperatures between TRPM8 and TRPV1.