Mammalian transient receptor potential (TRP) channels include non-selective cation channels such as TRPV1 that are activated by a range of different stimuli including, pH, vanilloids and heat (Caterina et al. 1997). It is likely that TRPV1 contributes to the perception of noxious heat. However, the channels involved in thermal sensation between 22 and 40 °C are less well understood and may involve a capsaicin-insensitive receptor (Nagy & Rang, 1999). We have used a combination of bioinformatics and molecular biology to identify novel vanilloid receptor-like channels that may be involved in thermal sensation. TRPV3 was identified as a polypeptide of 790 amino acids with 43 % amino acid identity to TRPV1. This receptor is identical to that recently published by several groups (e.g. Peier et al. 2002). Functional properties of this channel were investigated using whole-cell patch-clamp electrophysiology.

Chinese hamster ovary (CHO) cells were transiently transfected with 2 µg ml^-1 of human TRPV3 cDNA in a pIRES-eGFP vector. Transfected cells were grown on poly-D-lysine-coated glass coverslips and studied using whole-cell voltage-clamp electrophysiology. Temperature changes were generated using a rapid solution heater (MSDRL Research Engineering), over a range of 22-55 °C. All recordings were made at -60 mV in a solution of (mM): 1.67 CaCl₂, 1 MgCl₂, 2 KCl, 165 NaCl, 17 D-glucose and 10 Hepes; pH 7.3 (NaOH). Patch pipettes (borosillicate glass; 2-6 MV) were filled with (mM): 110 CsF, 30 TEA-Cl, 20 Cs-BAPTA, 2 ATP-Mg, 1 MgCl₂ and 10 Hepes; pH 7.2 (TEA-OH). Application of pH 5.5 or 10 µM capsaicin did not activate currents in TRPV3-expressing cells (-0.1 ± 2.3 pA, n = 5 and 2.5 ± 2.9 pA, n = 5, respectively; means ± S.E.M.). In contrast, increasing the temperature of the extracellular solution from 22 to 55 °C (2.8 °C s^-1) elicited inward currents (-158.9 ± 40.2 pA; n = 10) which were significantly greater than that in cells mock-transfected with empty pIRES-eGFP vector (-24.2 ± 3.9 pA; n = 8; P < 0.01, Student’s unpaired t test). Currents were activated at a threshold of ~38 °C (n = 10) and exhibited outward rectification (voltage ramps -80 to +80 mV, 320 mV s^-1) with a reversal potential of -6 mV, similar to TRPV1.

These data confirm that TRPV3 is a novel member of the TRPV family that can be activated by heat but not capsaicin or protons. The functional relevance of this channel subtype to thermal sensation and temperature regulation remains to be elucidated.