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Title: Modulation of the cold-activated cation channel TRPM8 by surface charge screening
Authors: Mahieu, Frank
Janssens, Annelies
Gees, Maarten
Talavera PĂ©rez, Karel
Nilius, Bernd
Voets, Thomas # ×
Issue Date: Jan-2010
Publisher: Cambridge University Press
Series Title: Journal of Physiology-London vol:588 issue:Pt 2 pages:315-324
Abstract: TRPM8, a cation channel activated by cold and by cooling agents such as menthol and icilin, is critically involved in somatosensory cold sensation. Ion fluxes through TRPM8 are highly sensitive to changes in extracellular Ca(2+) and pH, but the mechanisms underlying this type of modulation are poorly understood. Here we provide evidence that inhibition of TRPM8 currents by extracellular divalent cations and protons is due to surface charge screening. We demonstrate that increasing concentrations of divalent cations or protons cause parallel shifts of the voltage dependence of TRPM8 activation towards positive potentials. These shifts were interpreted using the Gouy-Chapman-Stern theory, yielding an estimate for the density of fixed negative surface charge between 0.0098 and 0.0126 equivalent charges per A(2). These results represent the first description of the effects of surface charge screening on a TRP channel and provide a straightforward explanation for the known effects of extracellular Ca(2+) on cold-sensitive neurons.
URI: 
ISSN: 0022-3751
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Ion Channel Research
Department of Materials Engineering - miscellaneous
Department of Cellular and Molecular Medicine - miscellaneous
× corresponding author
# (joint) last author

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