Intracellular ATP increases capsaicin-activated channel activity by interacting with nucleotide-binding domains

J. Kwak, Hyeon Wang Myeong Hyeon Wang, Sun Wook Hwang, T. Y. Kim, S. Y. Lee, U. Oh

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Capsaicin (CAP)-activated ion channel plays a key role in generating nociceptive neural signals in sensory neurons. Here we present evidence that intracellular ATP upregulates the activity of capsaicin receptor channel. In inside-out membrane patches isolated from sensory neurons, application of CAP activated a nonselective cation channel (i(cap)). Further addition of ATP to the bath caused a significant increase in i(cap), with a K(1/2) of 3.3 mM. Nonhydrolyzable analogs of ATP, adenylimidodiphosphate and adenosine 5'-O-(3-thio)-triphosphate, also increased i(cap). Neither Mg2+-free medium nor inhibitors of various kinases blocked the increase in i(cap) induced by ATP. The enhancing effect of ATP was also observed in inside-out patches of oocytes expressing vanilloid receptor 1, a cloned capsaicin receptor. Single point mutations (D178N, K735R) within the putative Walker type nucleotide-binding domains abolished the effect of ATP. These results show that ATP increases i(cap) in sensory neurons by direct interaction with the CAP channel without involvement of phosphorylation.

Original languageEnglish
Pages (from-to)8298-8304
Number of pages7
JournalJournal of Neuroscience
Volume20
Issue number22
Publication statusPublished - 2000 Nov 15
Externally publishedYes

Fingerprint

Capsaicin
Nucleotides
Adenosine Triphosphate
Sensory Receptor Cells
TRPV Cation Channels
Adenylyl Imidodiphosphate
Baths
Ion Channels
Point Mutation
Oocytes
Cations
Phosphotransferases
Up-Regulation
Phosphorylation
Membranes

Keywords

  • Allosteric regulation
  • ATP
  • Capsaicin receptor
  • Nucleotide-binding motif
  • Pain
  • VR1

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Kwak, J., Myeong Hyeon Wang, H. W., Hwang, S. W., Kim, T. Y., Lee, S. Y., & Oh, U. (2000). Intracellular ATP increases capsaicin-activated channel activity by interacting with nucleotide-binding domains. Journal of Neuroscience, 20(22), 8298-8304.

Intracellular ATP increases capsaicin-activated channel activity by interacting with nucleotide-binding domains. / Kwak, J.; Myeong Hyeon Wang, Hyeon Wang; Hwang, Sun Wook; Kim, T. Y.; Lee, S. Y.; Oh, U.

In: Journal of Neuroscience, Vol. 20, No. 22, 15.11.2000, p. 8298-8304.

Research output: Contribution to journalArticle

Kwak, J, Myeong Hyeon Wang, HW, Hwang, SW, Kim, TY, Lee, SY & Oh, U 2000, 'Intracellular ATP increases capsaicin-activated channel activity by interacting with nucleotide-binding domains', Journal of Neuroscience, vol. 20, no. 22, pp. 8298-8304.
Kwak, J. ; Myeong Hyeon Wang, Hyeon Wang ; Hwang, Sun Wook ; Kim, T. Y. ; Lee, S. Y. ; Oh, U. / Intracellular ATP increases capsaicin-activated channel activity by interacting with nucleotide-binding domains. In: Journal of Neuroscience. 2000 ; Vol. 20, No. 22. pp. 8298-8304.
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