Weiss Norbert, Arnoult Christophe, Feltz Anne, De Waard Michel
Inserm U607, Laboratoire Canaux Calciques, Fonctions et Pathologies, 17 Rue des Martyrs, Bâtiment C3, 38054 Grenoble Cedex 09, France.
Neurosci Res. 2006 Nov;56(3):332-43. doi: 10.1016/j.neures.2006.08.002. Epub 2006 Sep 12.
Direct G protein inhibition of N-type calcium channels is recognized by characteristic biophysical modifications. In this study, we quantify and simulate the importance of G protein dissociation on the phenotype of G protein-regulated whole-cell currents. Based on the observation that the voltage-dependence of the time constant of recovery from G protein inhibition is correlated with the voltage-dependence of channel opening, we depict all G protein effects by a simple kinetic scheme. All landmark modifications in calcium currents, except inhibition, can be successfully described using three simple biophysical parameters (extent of block, extent of recovery, and time constant of recovery). Modifications of these parameters by auxiliary beta subunits are at the origin of differences in N-type channel regulation by G proteins. The simulation data illustrate that channel reluctance can occur as the result of an experimental bias linked to the variable extent of G protein dissociation when peak currents are measured at various membrane potentials. To produce alterations in channel kinetics, the two most important parameters are the extents of initial block and recovery. These data emphasize the contribution of the degree and kinetics of G protein dissociation in the modification of N-type currents.
G蛋白对N型钙通道的直接抑制作用可通过特征性生物物理改变得以识别。在本研究中，我们对G蛋白解离对G蛋白调节的全细胞电流表型的重要性进行了量化和模拟。基于从G蛋白抑制作用恢复的时间常数的电压依赖性与通道开放的电压依赖性相关这一观察结果，我们用一个简单的动力学方案描述了所有G蛋白效应。除抑制作用外，钙电流中的所有标志性改变都可以用三个简单的生物物理参数（阻断程度、恢复程度和恢复时间常数）成功描述。辅助β亚基对这些参数的改变是G蛋白对N型通道调节存在差异的根源。模拟数据表明，当在不同膜电位下测量峰值电流时，通道电阻可能是与G蛋白解离可变程度相关的实验偏差导致的结果。为了产生通道动力学改变，两个最重要的参数是初始阻断程度和恢复程度。这些数据强调了G蛋白解离的程度和动力学在N型电流改变中的作用。
