The rat vanilloid receptor splice variant VR.5'sv blocks TRPV1 activation

The capsaicin receptor (VR1, TRPV1) 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 TRPV1 has been previously isolated and found to be insensitive to noxious stimuli. We report in this study that coexpression of VR.5'sv with TRPV1 in Xenopus oocytes blocks TRPV1-mediated current responses. Oocytes expressing the inhibitory profile demonstrated colocalization of TRPV1 and VR.5'sv-associated immunostaining in the plasma membrane. TRPV1 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 TRPV1 activation.