Modulation of the cold-activated cation channel TRPM8 by surface charge screening.

The Journal of Physiology
Frank MahieuThomas Voets

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.

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Citations

Jul 1, 2010·The Journal of Biological Chemistry·Frank J P KühnAndreas Lückhoff
Apr 12, 2012·The Journal of Biological Chemistry·María PertusaFélix Viana
Nov 1, 2011·Brain : a Journal of Neurology·Romina NassiniPierangelo Geppetti
May 28, 2013·Pflügers Archiv : European journal of physiology·Frank J P KühnAndreas Lückhoff
Sep 1, 2011·The Journal of Physiology·Annelies Janssens, Thomas Voets
Jul 1, 2015·The Journal of General Physiology·Balázs I TóthThomas Voets
May 19, 2018·Pharmaceuticals·Benedikt FelsAlbrecht Schwab

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