An alternative splicing product of the murine trpv1 gene dominant negatively modulates the activity of TRPV1 channels

Chunbo Wang, Hong Zhen Hu, Craig K. Colton, Jackie D. Wood, Michael X. Zhu

Research output: Contribution to journalArticlepeer-review

92 Scopus citations

Abstract

Transient receptor potential vanilloid 1 (TRPV1), or vanilloid receptor 1, is the founding member of the vanilloid type of TRP superfamily of nonselective cation channels. TRPV1 is activated by noxious heat, acid, and alkaloid irritants as well as several endogenous ligands and is sensitized by inflammatory factors, thereby serving important functions in detecting noxious stimuli in the sensory system and pathological states in different parts of the body. Whereas numerous studies have been carried out using the rat and human TRPV1 cDNA, the mouse TRPV1 cDNA has not been characterized. Here, we report molecular cloning of two TRPV1 cDNA variants from dorsal root ganglia of C57BL/6 mice. The deduced proteins are designated TRPV1α and TRPV1β and contain 839 and 829 amino acids, respectively. TRPV1β arises from an alternative intron recognition signal within exon 7 of the trpv1 gene. We found a predominant expression of TRPV1α in many tissues and significant expression of TRPV1β in dorsal root ganglia, skin, stomach, and tongue. When expressed in HEK 293 cells or Xenopus oocytes, TRPV1α formed a Ca2+-permeable channel activated by ligands known to stimulate TRPV1. TRPV1β was not functional by itself but its co-expression inhibited the function of TRPV1α. Furthermore, although both isoforms were synthesized at a similar rate, less TRPV1β than TRPV1α protein was found in cells and on the cell surface, indicating that the β isoform is highly unstable. Our data suggest that TRPV1β is a naturally occurring dominant-negative regulator of the responses of sensory neurons to noxious stimuli.

Original languageEnglish
Pages (from-to)37423-37430
Number of pages8
JournalJournal of Biological Chemistry
Volume279
Issue number36
DOIs
StatePublished - Sep 3 2004

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