A multi-ion permeation mechanism in neuronal background chloride channels.
A multi-ion permeation mechanism in neuronal background chloride channels.
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DOI：
10.1085/jgp.104.4.725
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发表时间：
1994-10
期刊：
影响因子：
--
通讯作者：
Nonner W
中科院分区：
文献类型：
--
作者：
Franciolini F;Nonner W
在不同的NaCl梯度和绝对浓度下，测定了大鼠海马神经元背景Cl通道的单一电流/电压关系。通道显示出Cl和Na离子的渗透性。当盐浓度从300 mM到600 mM对称增加时，观察到统一电导的超线性增加，表明多离子渗透机制。根据实验电流/电压关系测试了多种渗透动力学模型。要重现所有的测量结果，必须建立一个由多达五个离子的混合络合物占据的孔的模型。最小模型包括4个平衡态和4个速率限制跃迁，使得空孔首先接受一个阴离子，然后可以获得一个或两个阳离子/阴离子对。形成了三个输运循环：慢阴离子循环（在空和单阴离子状态之间），慢阳离子循环（在一离子和三离子状态之间）和快阴离子循环（在三离子和五离子状态之间）。因此，渗透阴离子是阳离子渗透所必需的，几个结合的阴离子和阳离子促进了阴离子的高渗透率。优化后的自由能和电荷参数产生了自一致的分子解释，这可以解释孔从溶液中接受离子的特定顺序。虽然该模型描述了在高浓度下观察到的通道的混合阴离子/阳离子渗透性，但它预测了生理离子条件下Cl阴离子的高选择性。
Unitary current/voltage relationships of background Cl channels of rat hippocampal neurons were determined for varied gradients and absolute concentrations of NaCl. The channels revealed permeabilities for both Cl and Na ions. A hyperlinear increase of unitary conductance, observed for a symmetrical increase of salt concentration from 300 and 600 mM, indicated a multi-ion permeation mechanism. A variety of kinetic models of permeation were tested against the experimental current/voltage relationships. Models involving a pore occupied by mixed complexes of up to five ions were necessary to reproduce all measurements. A minimal model included four equilibrium states and four rate-limiting transitions, such that the empty pore accepts first an anion and then can acquire one or two cation/anion pairs. Three transport cycles are formed: a slow anion cycle (between the empty and single-anion states), a slow cation cycle (between the one- and three-ion states), and a fast anion cycle (between the three- and five-ion states). Thus, permeant anions are required for cation permeation, and several bound anions and cations promote a high rate of anion permeation. The optimized free- energy and electrical charge parameters yielded a self-consistent molecular interpretation, which can account for the particular order in which the pore accepts ions from the solutions. Although the model describes the mixed anion/cation permeability of the channel observed at elevated concentrations, it predicts a high selectivity for Cl anion at physiological ionic conditions.