Extensive co-localization and heteromultimer formation of the vanilloid receptor-like protein TRPV2 and the capsaicin receptor TRPV1 in the adult rat cerebral cortex.

The capsaicin receptor TRPV1, a member of the transient receptor potential (TRP) family of calcium-selective ion channels, responds to noxious stimuli and is predominantly expressed in nociceptive neurons. The homologous receptor TRPV2 shows wide tissue distribution including some sensory neurons, where it is proposed to function as a heat sensor or a growth-factor-activated channel. Members of the TRP family of channels have been shown to interact, resulting in hybrid channels with new properties. We examined the possibility of multimer formation between TRPV1 and TRPV2, using biochemical techniques. We present evidence that TRPV1 and TRPV2 can heteromultimerize efficiently in vitro. By using immunohistochemistry we detected co-localization of the two receptors in rat dorsal root ganglia. TRPC4 transcripts are also detected in capsaicin-sensitive dorsal root ganglia neurons. We extended the search for TRPV1-TRPV2 co-localization in the brain, where we detected extensive co-expression of the two receptors in the IV, V and VI layer neurons of the adult rat cerebral cortex. Co-immunoprecipitation experiments confirmed the interaction of the two receptors in vivo, indicating heteromultimer formation in native tissue. Formation of heteromultimers between vanilloid receptors may increase the functional diversity of this receptor family.