Extracellular zinc ion inhibits ClC-0 chloride channels by facilitating slow gating
Extracellular zinc ion inhibits ClC-0 chloride channels by facilitating slow gating
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DOI：
10.1085/jgp.112.6.715
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发表时间：
1998-12-01
影响因子：
3.8
通讯作者：
Chen, TY
中科院分区：
文献类型：
--
作者：
Chen, TY
细胞外Zn ~（2+）可逆性抑制ClC-0 Cl ~-通道。抑制的表观开启和关闭速率是高度温度敏感的，表明Zn 2+对ClC-0的慢门控（或失活）的影响。在不存在Zn 2+的情况下，慢门控弛豫的速率随温度而增加，Q（10）类似于37。胞外Zn ~（2+）在所有温度下均能促进慢门控过程，但Q（10）没有变化。对慢门控过程速率常数的进一步分析表明，Zn ~（2+）主要影响慢门控的前向速率（失活速率），而不是后向速率（失活恢复速率）。当ClC-0与Zn 2+结合时，慢门控过程的平衡常数增加了约30倍，反映了失活通道中的Zn 2+亲和力比开放状态通道高30倍。通过广泛的膜电位检查，锌2+抑制打开的慢门在所有电压下具有相同的效力，这表明一个两态模型是不足以描述的慢门控过渡。遵循最初由Pusch及其同事提出的模型（Pusch，M.，联合Ludewig和T.J. Jentsch。1997. J.Gen.Physiol.109：105-116），Zn 2+对慢门激活曲线的影响可以通过增加两个限制来很好地描述：（a）Zn 2+结合到开放通道的解离常数为30 μ M，和（B）对于Zn 2+结合的通道，慢门过程的开放状态和过渡状态之间的熵差增加了27 J/ mol/度K。这些结果共同表明，胞外Zn 2+通过促进慢门控过程抑制ClC-0。
Extracellular Zn2+ was found to reversibly inhibit the ClC-0 Cl- channel. The apparent on and off rates of the inhibition were highly temperature sensitive, suggesting an effect of Zn2+ on the slow gating (or inactivation) of ClC-0. In the absence of Zn2+, the rate of the slow-gating relaxation increased with temperature, with a Q(10) of similar to 37. Extracellular Zn2+ facilitated the slow-gating process at all temperatures, but the Q(10) did not change. Further analysis of the rate constants of the slow-gating process indicates that the effect of Zn2+ is mostly on the forward rate (the rate of inactivation) rather than the backward rate (the rate of recovery from inactivation) of the slow gating. When ClC-0 is bound with Zn2+, the equilibrium constant of the slow-gating process is increased by similar to 30-fold, reflecting a 30-fold higher Zn2+ affinity in the inactivated channel than in the open-state channel. As examined through a wide range of membrane potentials, Zn2+ inhibits the opening of the slow gate with equal potency at all voltages, suggesting that a two-state model is inadequate to describe the slow-gating transition. Following a model originally proposed by Pusch and co-workers (Pusch, M., U. Ludewig, and T.J. Jentsch. 1997. J. Gen. Physiol. 109:105-116), the effect of Zn2+ on the activation curve of the slow gate can be well described by adding two constraints: (a) the dissociation constant for Zn2+ binding to the open channel is 30 mu M, and (b) the difference in entropy between the open state and the transition state of the slow-gating process is increased by 27 J/ mol/degrees K for the Zn2+-bound channel. These results together indicate that extracellular Zn2+ inhibits ClC-0 by facilitating the slow-gating process.