Leuchtag H R
Department of Biology, Texas Southern University, Houston 77004.
Biophys J. 1994 Jan;66(1):217-24. doi: 10.1016/S0006-3495(94)80757-X.
Forces acting on the S4 segments of the channel, the voltage-sensing structures, are analyzed. The conformational change in the Na channel is modeled as a helix-coil transition in the four S4 segments, coupled to the membrane voltage by electrical forces. In the model, repulsions between like charges make the S4 segment unstable, but field-dependent forces hold it in an alpha-helix configuration at resting potential. At threshold depolarization, the S4 helices cooperatively expand into random coils, breaking the hydrogen bonds connecting adjacent loops of the alpha helices. Exposed electron pairs left on the carbonyl oxygens constitute sites at which cations can bind selectively. The first hydrogen bond to break is at the channel exterior, then the second breaks, and so on in a zipper-like motion along the entire segment. The Na+ ions hop from one site to the next until all H bonds are broken and all sites are filled with ions. This completes the pathway over which the permeant ions move through the channel, driven by the electrochemical potential difference across the membrane. This microscopic mechanism is consistent with the thermodynamic explanation of ion-channel gating previously formulated as the ferroelectric-superionic transition hypothesis.
分析作用于通道电压感应结构S4片段上的力。钠通道中的构象变化被模拟为四个S4片段中的螺旋-卷曲转变，并通过电力与膜电压耦合。在该模型中，同性电荷之间的排斥使S4片段不稳定，但场依赖力使其在静息电位下保持α螺旋构型。在阈值去极化时，S4螺旋协同扩展成无规卷曲，打破连接α螺旋相邻环的氢键。羰基氧上留下的暴露电子对构成阳离子可以选择性结合的位点。首先断裂的氢键在通道外部，然后第二个氢键断裂，等等，沿着整个片段以拉链状运动进行。Na+离子从一个位点跳跃到下一个位点，直到所有氢键都断裂且所有位点都被离子填充。这就完成了渗透离子在跨膜电化学势差驱动下通过通道的路径。这种微观机制与先前作为铁电-超离子转变假说提出的离子通道门控的热力学解释一致。
