Contribution of TRPV1-TRPA1 interaction to the single channel properties of the TRPA1 channel

Alexander Staruschenko, Nathaniel Jeske, Armen N Akopian

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

Several lines of evidence suggest that TRPA1 and TRPV1 mutually control the transduction of inflammation-induced noxious stimuli in sensory neurons. It was recently shown that certain TRPA1 properties are modulated by TRPV1. However, direct interaction between TRPA1 and TRPV1 as well as regulation of TRPA1 intrinsic characteristics by the TRPV1 channel have not been examined. To address these questions, we have studied a complex formation between TRPA1 and TRPV1 and characterized the influence of TRPV1 on single channel TRPA1-mediated currents. Co-immunoprecipitation analysis revealed direct interactions between TRPA1 and TRPV1 in an expression system as well as in sensory neurons. Data generated with total internal reflection fluorescence-based fluorescence resonance energy transfer indicate that a TRPA1-TRPV1 complex can be formed on the plasma membrane. The fluorescence resonance energy transfer interaction between TRPA1 and TRPV1 channels is as effective as for TRPV1 or TRPA1 homomers. Single channel analysis in a heterologous expression system and in sensory neurons of wild type and TRPV1 knockout mice demonstrated that co-expression of TRPV1 with TRPA1 results in outward rectification of single channel mustard oil (IMO) current-voltage relationships (I-V) and substantial modulation of the open probability at negative holding potentials. TRPV1 also does not influence the characteristics of single channel IMO in Ca 2+-free extracellular solution. However, association of TRPA1 with TRPV1 was not affected in Ca2+-free media. To assess a role of intracellular Ca2+ in TRPV1-dependent modulation of TRPA1 modulation, the TRPA1-mediated single channel WIN55,212-2-gated current (IWIN) was recorded in inside-out configuration. Our data indicate that single channel properties of TRPA1 are regulated by TRPV1 independently of intracellular Ca2+. In summary, our results support the hypothesis that TRPV1 and TRPA1 form a complex and that TRPV1 influences intrinsic characteristics of the TRPA1 channel.

Original languageEnglish (US)
Pages (from-to)15167-15177
Number of pages11
JournalJournal of Biological Chemistry
Volume285
Issue number20
DOIs
StatePublished - May 14 2010

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Sensory Receptor Cells
Neurons
Fluorescence Resonance Energy Transfer
Modulation
Cell membranes
Immunoprecipitation
Knockout Mice
Fluorescence
Cell Membrane
Inflammation
Electric potential

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Contribution of TRPV1-TRPA1 interaction to the single channel properties of the TRPA1 channel. / Staruschenko, Alexander; Jeske, Nathaniel; Akopian, Armen N.

In: Journal of Biological Chemistry, Vol. 285, No. 20, 14.05.2010, p. 15167-15177.

Research output: Contribution to journalArticle

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