Molecular Neurophysiology Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
Biophys J. 2010 Nov 3;99(9):2863-9. doi: 10.1016/j.bpj.2010.08.053.
For ion channels, the transmembrane potential plays a critical role by acting as a driving force for permeant ions. At the microscopic level, the transmembrane potential is thought to decay nonlinearly across the ion permeation pathway because of the irregular three-dimensional shape of the channel's pore. By taking advantage of the current structural and functional understanding of cyclic nucleotide-gated channels, in this study we experimentally explore the transmembrane potential's distribution across the open pore. As a readout for the voltage drop, we engineered cysteine residues along the selectivity filter and scanned the sensitivity of their modification rates by Ag(+) to the transmembrane potential. The experimental data, which indicate that the majority of the electric field drops across the selectivity filter, are in good agreement with continuum electrostatic calculations using a homology model of an open CNG channel. By focusing the transmembrane potential across the selectivity filter, the electromotive driving force is coupled with the movement of permeant ions in the filter, maximizing the efficiency of this process.
对于离子通道，跨膜电位起着关键作用，它作为可渗透离子的驱动力。在微观水平上，由于通道孔的不规则三维形状，跨膜电位被认为在离子渗透途径中呈非线性衰减。本研究利用对环核苷酸门控通道的当前结构和功能的理解，实验性地探索了跨膜电位在开放孔中的分布。作为电压降的读出，我们沿着选择性过滤器设计了半胱氨酸残基，并通过 Ag(+)扫描其修饰速率对跨膜电位的敏感性。实验数据表明，大部分电场降落在选择性过滤器上，与使用开放 CNG 通道同源模型进行的连续静电计算吻合良好。通过将跨膜电位集中在选择性过滤器上，电动驱动力与过滤器中可渗透离子的运动相耦合，从而最大限度地提高该过程的效率。
