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PMID: 19404398 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Inorganic polyphosphate modulates TRPM8 channels.

PloS one ·Vol. 4 ·No. 4 ·2009-00-00 ·Pages e5404

Zakharian E, Thyagarajan B, French RJ, Pavlov E, Rohacs T

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)P(2)). 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.

MeSH Terms
Acid Anhydride Hydrolases/metabolism Cell Line Humans Hydroxybutyrates/metabolism Polyesters/metabolism Polyphosphates/pharmacology Prohibitins Protein Binding Protein Stability TRPM Cation Channels/metabolism
Chemicals
Hydroxybutyrates PHB protein, human Polyesters Polyphosphates Prohibitins TRPM Cation Channels TRPM8 protein, human poly-beta-hydroxybutyrate Acid Anhydride Hydrolases exopolyphosphatase
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Zakharian Eleonora
Department of Pharmacology and Physiology, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey, United States of America.
Thyagarajan Baskaran
French Robert J
Pavlov Evgeny
Rohacs Tibor
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Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0005404
Published
2009-00-00
Epub
2009-00-30
Pages
e5404
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC2671608
Subset
IM
Grants
NINDS NIH HHS · R01 NS055159 · United States
NINDS NIH HHS · NS055159 · United States
External Links
PubMed source DOI: 10.1371/journal.pone.0005404 PMC Full Text View journal details
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