Inorganic polyphosphate modulates TRPM8 channels

Eleonora Zakharian, Baskaran Thyagarajan, Robert J. French, Evgeny Pavlov, Tibor Rohacs

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Polyphosphate (polyP) is an inorganic polymer built of tens to hundreds of phosphates, linked by high-energy phosphoanhydride bonds. PolyP forms complexes and modulates activities of many proteins including ion channels. Here we investigated the role of polyP in the function of the transient receptor potential melastatin 8 (TRPM8) channel. Using whole-cell patch-clamp and fluorescent calcium measurements we demonstrate that enzymatic breakdown of polyP by exopolyphosphatase (scPPX1) inhibits channel activity in human embryonic kidney and F-11 neuronal cells expressing TRPM8. We demonstrate that the TRPM8 channel protein is associated with polyP. Furthermore, addition of scPPX1 altered the voltage-dependence and blocked the activity of the purified TRPM8 channels reconstituted into planar lipid bilayers, where the activity of the channel was initiated by cold and menthol in the presence of phosphatidylinositol 4,5-biphosphate (PtdIns(4,5)P2). The biochemical analysis of the TRPM8 protein also uncovered the presence of poly-(R)-3-hydroxybutyrate (PHB), which is frequently associated with polyP. We conclude that the TRPM8 protein forms a stable complex with polyP and its presence is essential for normal channel activity.

Original languageEnglish (US)
Title of host publicationInorganic Chemistry
Subtitle of host publicationReactions, Structure and Mechanisms
PublisherApple Academic Press
Pages11-35
Number of pages25
ISBN (Electronic)9781466559776
ISBN (Print)9781926692593
StatePublished - Jan 1 2011

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Polyphosphates
Phosphatidylinositol 4,5-Diphosphate
Proteins
Menthol
Inorganic polymers
Lipid bilayers
3-Hydroxybutyric Acid
Clamping devices
Ion Channels
Phosphates
Cells
Calcium
Electric potential

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Zakharian, E., Thyagarajan, B., French, R. J., Pavlov, E., & Rohacs, T. (2011). Inorganic polyphosphate modulates TRPM8 channels. In Inorganic Chemistry: Reactions, Structure and Mechanisms (pp. 11-35). Apple Academic Press.

Inorganic polyphosphate modulates TRPM8 channels. / Zakharian, Eleonora; Thyagarajan, Baskaran; French, Robert J.; Pavlov, Evgeny; Rohacs, Tibor.

Inorganic Chemistry: Reactions, Structure and Mechanisms. Apple Academic Press, 2011. p. 11-35.

Research output: Chapter in Book/Report/Conference proceedingChapter

Zakharian, E, Thyagarajan, B, French, RJ, Pavlov, E & Rohacs, T 2011, Inorganic polyphosphate modulates TRPM8 channels. in Inorganic Chemistry: Reactions, Structure and Mechanisms. Apple Academic Press, pp. 11-35.
Zakharian E, Thyagarajan B, French RJ, Pavlov E, Rohacs T. Inorganic polyphosphate modulates TRPM8 channels. In Inorganic Chemistry: Reactions, Structure and Mechanisms. Apple Academic Press. 2011. p. 11-35
Zakharian, Eleonora ; Thyagarajan, Baskaran ; French, Robert J. ; Pavlov, Evgeny ; Rohacs, Tibor. / Inorganic polyphosphate modulates TRPM8 channels. Inorganic Chemistry: Reactions, Structure and Mechanisms. Apple Academic Press, 2011. pp. 11-35
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