Nilius Bernd, Prenen Jean, Droogmans Guy, Voets Thomas, Vennekens Rudi, Freichel Marc, Wissenbach Ulrich, Flockerzi Veit
Department of Physiology, Campus Gasthuisberg, KU Leuven, Leuven B-3000, Belgium.
J Biol Chem. 2003 Aug 15;278(33):30813-20. doi: 10.1074/jbc.M305127200. Epub 2003 Jun 10.
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.
TRPM4是一种Ca2+激活但Ca2+不可通透的阳离子通道。细胞内Ca2+浓度（[Ca2+]i）升高会诱导TRPM4通道激活并使电流随后减小。这种失活在无细胞片膜中显著降低。在全细胞和无细胞配置中，通过TRPM4的电流在负电位时迅速失活。在正电位时，电流大得多且激活缓慢。这种电压依赖性行为导致稳态电流出现明显的外向整流。从预脉冲到正电位后的尾电流幅度得出的瞬时电流-电压关系是线性的。电流呈现玻尔兹曼类型的激活；开放通道的比例在正电位时增加，在负电位时较低。电压依赖性并非由于二价阳离子的阻断或细胞内Ca2+与激活位点的电压依赖性结合，这表明TRPM4是一种具有内在电压传感机制的瞬时受体电位通道。TRPM4的电压依赖性可能在功能上很重要，尤其是在产生平台样或爆发性动作电位的可兴奋组织中。
