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• W2095642680 endingPage "651" @default.
• W2095642680 startingPage "641" @default.
• W2095642680 abstract "The opening and closing of chloride (Cl-) channels in the ClC family are thought to tightly couple to ion permeation through the channel pore. In the prototype channel of the family, the ClC-0 channel from the Torpedo electric organ, the opening-closing of the pore in the millisecond time range known as fast gating is regulated by both external and internal Cl- ions. Although the external Cl- effect on the fast-gate opening has been extensively studied at a quantitative level, the internal Cl- regulation remains to be characterized. In this study, we examine the internal Cl- effects and the electrostatic controls of the fast-gating mechanism. While having little effect on the opening rate, raising [Cl-]i reduces the closing rate (or increases the open time) of the fast gate, with an apparent affinity of >1 M, a value very different from the one observed in the external Cl- regulation on the opening rate. Mutating charged residues in the pore also changes the fast-gating properties-the effects are more prominent on the closing rate than on the opening rate, a phenomenon similar to the effect of [Cl-]i on the fast gating. Thus, the alteration of fast-gate closing by charge mutations may come from a combination of two effects: a direct electrostatic interaction between the manipulated charge and the negatively charged glutamate gate and a repulsive force on the gate mediated by the permeant ion. Likewise, the regulations of internal Cl- on the fast gating may also be due to the competition of Cl- with the glutamate gate as well as the overall more negative potential brought to the pore by the binding of Cl-. In contrast, the opening rate of the fast gate is only minimally affected by manipulations of [Cl-]i and charges in the inner pore region. The very different nature of external and internal Cl- regulations on the fast gating thus may suggest that the opening and the closing of the fast gate are not microscopically reversible processes, but form a nonequilibrium cycle in the ClC-0 fast-gating mechanism." @default.
• W2095642680 created "2016-06-24" @default.
• W2095642680 creator A5011321854 @default.
• W2095642680 creator A5063658779 @default.
• W2095642680 creator A5016822847 @default.
• W2095642680 date "2003-10-27" @default.
• W2095642680 modified "2023-09-26" @default.
• W2095642680 title "Electrostatic Control and Chloride Regulation of the Fast Gating of ClC-0 Chloride Channels" @default.
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• W2095642680 doi "https://doi.org/10.1085/jgp.200308846" @default.
• W2095642680 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2229583" @default.
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• W2095642680 hasPublicationYear "2003" @default.
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