The rat vanilloid receptor splice variant VR.5′sv blocks TRPVI activation

The capsaicin receptor (VRI, TRPVI) is a ligand-gated ion channel predominantly expressed in peripheral nociceptors and activated by multiple noxious stimuli including products of inflammation. A 5'-splice variant (VR.5'sv) of TRPVI has been previously isolated and found to be insensitive to noxious stimuli. We report in this study that coexpression of VR.5'sv with TRPVI in Xenopus oocytes blocks TRPVI-mediated current responses. Oocytes expressing the inhibitory profile demonstrated colocalization of TRPVI and VR.5'sv-associated immunostaining in the plasma membrane. TRPVI protein expression was comparable in all groups. Evidence of endogenous VR.5'-splice variant-like-protein expression was detected in dorsal root ganglion. These results support the idea that coexpression of VR.5'sv or a similar variant could result in inhibitory modulation of TRPVI activation.