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TRPV3 is a calcium-permeable temperature-sensitive cation channel

Nature volume 418, pages 181–186 (2002)Cite this article

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 °C; TRPV1 (ref. 1)), noxious heat (>52 °C; TRPV2 (ref. 2)), and cooling (< 22 °C; TRPM8 (refs 3, 4)) have been cloned; however, little is known about the molecular determinants of temperature sensing in the range between ∼22 °C and 40 °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 °C to 40 °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 cooling5,6,7,8,9,10. On the basis of these properties, we propose that hTRPV3 is thermosensitive in the physiological range of temperatures between TRPM8 and TRPV1.

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Figure 1: Deduced primary amino acid sequence of hTRPV3 and alignment with hTRPV1 and hTRPV2.
Figure 2: In situ hybridization of monkey tissue sections showing expression of TRPV3 in central and peripheral neurons and in the skin.
Figure 3: Temperature-activated currents and [Ca2+]i increases in hTRPV3-expressing CHO-K1 cells. *
Figure 4: Temperature-activated hTRPV3 currents. *
Figure 5: Temperature-dependent gating of IhTRPV3.

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Notes

  1. * Figures 3e and 4d were published incorrectly in the AOP version of this paper on 23 June 2002. In the AOP publication, the blue trace in Fig. 3e was labelled incorrectly as 'NMDG+ (30 mM Ca2+)' and the red trace was labelled incorrectly as 'NMDG+ (0 mM Ca2+)'. Likewise, in Fig. 4d, the second trace from the top was incorrectly labelled as '+60 mV'. These errors were corrected on 11 July 2002.

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Acknowledgements

We thank U. Berger, L. Yue, X. Wei, W. Yu, A. Kabakov, L. Runnels, J. Pulido, W. Cao and H. Ferriera for assistance. We are grateful to S. Glucksmann, O. Tayber, L. DeFelice and members of Clapham laboratory for discussion and comments.

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Author notes

  1. Peter S. DiStefano & Rory Curtis

    Present address: Elixir Pharmaceuticals Inc., 1000, One Kendall Square, Cambridge, Massachusetts, 02139, USA

  2. Haoxing Xu, I. Scott Ramsey, Suhas A. Kotecha, Deborah Lawson, Pei Ge, Jeremiah Lilly, Inmaculada Silos-Santiago, Yu Xie, Peter S. DiStefano and Rory Curtis: These authors contributed equally to this work

Authors and Affiliations

  1. Howard Hughes Medical Institute, Children's Hospital, Harvard Medical School, Enders 1309, 320 Longwood Avenue, Boston, Massachusetts, 02115, USA

    Haoxing Xu, I. Scott Ramsey, Suhas A. Kotecha, Jayhong A. Chong & David E. Clapham

  2. Program in Neuroscience, Harvard Medical School, Goldenson Building B2-228, 220 Longwood Avenue, Boston, Massachusetts, 02115, USA

    Magdalene M. Moran

  3. Millennium Pharmaceuticals Inc., 75 Sidney Street, Cambridge, Massachusetts, 02139, USA

    Deborah Lawson, Pei Ge, Jeremiah Lilly, Inmaculada Silos-Santiago, Yu Xie, Peter S. DiStefano & Rory Curtis

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Correspondence to David E. Clapham.

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Competing interests

D.L., P.G., J.L., I.S.-S., P.S.D., Y.X. and R.C. were all employees of Millennium Pharmaceuticals during the programme of work, and these individuals may hold stocks in Millennium.

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Xu, H., Ramsey, I., Kotecha, S. et al. TRPV3 is a calcium-permeable temperature-sensitive cation channel. Nature 418, 181–186 (2002). https://doi.org/10.1038/nature00882

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