Voltage dependence of the Ca2+-activated cation channel TRPM4.
TRPM4 is a Ca2+-activated but Ca2+-impermeable cation channel. An increase of [Ca2+]i induces activation and subsequent reduction of currents through TRPM4 channels. This inactivation is strikingly decreased in cell-free patches. In whole cell and cell-free configuration, currents through TRPM4 deactivate rapidly at negative potentials. At positive potentials, currents are much larger and activate slowly. This voltage-dependent behavior induces a striking outward rectification of the steady state currents. The instantaneous current-voltage relationship, derived from the amplitude of tail currents following a prepulse to positive potentials, is linear. Currents show a Boltzmann type of activation; the fraction of open channels increases at positive potentials and is low at negative potentials. Voltage dependence is not due to block by divalent cations or to voltage-dependent binding of intracellular Ca2+ to an activator site, indicating that TRPM4 is a transient receptor potential channel with an intrinsic voltage-sensing mechanism. Voltage dependence of TRPM4 may be functionally important, especially in excitable tissues generating plateau-like or bursting action potentials.
Nilius
Bernd
B
Department of Physiology, Campus Gasthuisberg, KU Leuven, Leuven B-3000, Belgium. bernd.nilius@med.kuleuven.ac.be
Prenen
Jean
J
Droogmans
Guy
G
Voets
Thomas
T
Vennekens
Rudi
R
Freichel
Marc
M
Wissenbach
Ulrich
U
Flockerzi
Veit
V
D000200:Action Potentials / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics* / Q000378:metabolism*; D027682:Cation Transport Proteins; D002460:Cell Line; D018076:DNA, Complementary; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D007668:Kidney / Q000166:cytology; D051379:Mice; D008969:Molecular Sequence Data; D018408:Patch-Clamp Techniques; D050053:TRPM Cation Channels; D014162:Transfection
D015220:Calcium Channels; D027682:Cation Transport Proteins; D018076:DNA, Complementary; D050053:TRPM Cation Channels; C437888:TRPM4 protein, human; D002118:Calcium