Modulation of the cold-activated cation channel TRPM8 by surface charge screening.
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.
Mahieu
Frank
F
KU Leuven, Laboratory of Ion Channel Research, Department of Molecular Cell Biology, Leuven, Belgium.
Janssens
Annelies
A
Gees
Maarten
M
Talavera
Karel
K
Nilius
Bernd
B
Voets
Thomas
T
D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D004594:Electrophysiology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D050053:TRPM Cation Channels / Q000378:metabolism*
D050053:TRPM Cation Channels; C425966:TRPM8 protein, human; D002118:Calcium