电压门控离子通道离子选择性的广义微观理论
Generalized microscopic theory of ion selectivity in voltage-gated ion channels
摘要：
离子通道是存在于活细胞膜中的特定蛋白质。它们控制特定离子通过细胞的流动，由离子通道的电化学梯度启动。在此过程中，它们控制着重要的生理过程，如肌肉收缩和神经元连接，如果这些通道失控，这些过程就无法正常激活，从而导致危及生命的疾病和心理障碍。在这里，我们将开发一个广义的离子选择性的微观理论适用于KcsA，Na $_{\rm v}$ Rh和Ca $_{\rm v}$（L型）离子通道。我们明确地揭示了为什么以及如何一个给定的离子通道可以是高度选择性的，但具有每秒一百万离子或更高的电导率。我们将确定并证明正确的物理生化机制，负责在给定的离子通道中的特定离子的高选择性。上述机制由五个条件组成，其可以直接与这些参数相关-（i）脱水能量，（ii）“正确”离子的浓度，（iii）库仑-范德华吸引力，（iv）孔和离子尺寸，以及间接与（v）热力学稳定性和（vi）“撞击”辅助渗透相关。
英文摘要：
Ion channels are specific proteins present in the membranes of living cells. They control the flow of specific ions through a cell, initiated by an ion channel's electrochemical gradient. In doing so, they control important physiological processes such as muscle contraction and neuronal connectivity, which cannot be properly activated if these channels go haywire, leading to life-threatening diseases and psychological disorders. Here, we will develop a generalized microscopic theory of ion selectivity applicable to KcsA, Na$_{\rm v}$Rh and Ca$_{\rm v}$ (L-type) ion channels. We unambiguously expose why and how a given ion-channel can be highly selective, and yet has a conductance of the order of one million ions per second, or higher. We will identify and prove the correct physico-biochemical mechanisms that are responsible for the high selectivity of a particular ion in a given ion channel. The above mechanisms consist of five conditions, which can be directly associated to these parameters - (i) dehydration energy, (ii) concentration of the "correct" ions (iii) Coulomb-van-der-Waals attraction, (iv) pore and ionic sizes, and indirectly to (v) the thermodynamic stability and (vi) the "knock-on" assisted permeation.
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