Leuchtag H R
Department of Biology, Texas Southern University, Houston 77004.
Biophys J. 1992 Apr;62(1):22-4. doi: 10.1016/S0006-3495(92)81766-6.
Many investigators assert that the ion-conducting pathway of the Na channel is a water-filled pore. This assertion must be reevaluated to clear the way for more productive approaches to channel gating. The hypothesis of an aqueous pore leaves the questions of voltage-dependent gating and ion selectivity unexplained because a column of water can neither serve as a switch nor provide the necessary selectivity. The price of believing in an aqueous pore therefore is a futile search for separate ad hoc mechanisms for gating and selectivity. The fallacy is to assume that only water is available to carry ions rapidly, ignoring the role of the glycoprotein, which can form an elastomeric phase with water. The elastomer is a state of matter, neither liquid nor solid, in which the molecules of a liquid are threaded together with cross-linked polymer chains; it supports fast ion motion (Owen, 1989). An alternative hypothesis for channel gating, based on condensed-state materials science, already exists (Leuchtag, 1988, 1991a). The ferroelectric-superionic transition hypothesis (FESITH) postulates that the Na channel exists in a metastable ordered (closed) state at resting potential and, on threshold depolarization, undergoes a reversible order-disorder phase transition to a less-ordered, ion-conducting (open) state. The ordered state is ferroelectric; the disordered state is a fast ion conductor selective for Li+ and Na+. The basis of the voltage dependence is elevation of transition temperature with electric field, well established in ferroelectrics. FESITH is consistent with single-channel transitions, gating currents, heat and cold block, and other phenomena observed at channel or membrane level. An implication of FESITH, the Curie-Weiss law, has been shown to explain existing data on membrane capacitance versus temperature in squid axon (Leuchtag, 1991c). Only on the basis of a clear understanding of function can we expect new structural data on the Na-channel glycoprotein to generate realistic structure-function models at the molecular level.
许多研究者断言，钠通道的离子传导途径是一个充满水的孔道。必须重新评估这一断言，以便为更有效的通道门控研究方法扫清道路。水相孔道的假说无法解释电压依赖性门控和离子选择性问题，因为一列水既不能用作开关，也不能提供必要的选择性。因此，相信水相孔道的代价是徒劳地寻找单独的门控和选择性的特殊机制。错误在于假设只有水能够快速携带离子，而忽略了糖蛋白的作用，糖蛋白可以与水形成弹性体相。弹性体是一种物质状态，既不是液体也不是固体，其中液体分子与交联聚合物链交织在一起；它支持快速离子运动（欧文，1989）。基于凝聚态材料科学的通道门控替代假说已经存在（勒奇塔格，1988年、1991年a）。铁电-超离子转变假说（FESITH）假定，钠通道在静息电位下以亚稳态有序（关闭）状态存在，在阈值去极化时，经历可逆的有序-无序相变，转变为无序的、离子传导（开放）状态。有序状态是铁电的；无序状态是对Li+和Na+有选择性的快速离子导体。电压依赖性的基础是电场使转变温度升高，这在铁电体中已得到充分证实。FESITH与单通道转变、门控电流、热和冷阻断以及在通道或膜水平观察到的其他现象一致。FESITH的一个推论，居里-外斯定律，已被证明可以解释鱿鱼轴突中膜电容与温度的现有数据（勒奇塔格，1991年c）。只有在清楚理解功能的基础上，我们才能期望关于钠通道糖蛋白的新结构数据在分子水平上生成现实的结构-功能模型。
