Key result
Mutations at K149 in the ClC-0 chloride channel alter the voltage and chloride dependence of fast gating, likely due to electrostatic contributions to chloride binding.
The conserved lysine K149 in the ClC-0 chloride channel plays a key role in fast-gate opening through electrostatic contributions to chloride binding.
Does not alter clinical management of channelopathies; extends biophysical model of ClC fast gating in non-mammalian systems.
ClC-0 is a chloride channel whose gating is sensitive to voltage, chloride, and pH. In a previous publication, we showed that the K149C mutation causes a +70-mV shift in the voltage dependence of ClC-0 fast gating. In this paper we analyze the effects of a series of mutations at K149 on the voltage and chloride dependence of gating. By fitting our data to the previously proposed four-state model for ClC-0 fast gating, we show which steps in fast-gate opening are likely to be affected by these mutations. Computational analysis of mutant ClC-0 homology models show electrostatic contributions to chloride binding that may partially account for the effects of K149 on gating. The analysis of gating kinetics in combination with the available structural information suggests some of the structural changes likely to underpin fast-gate opening.
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Engh et al. (2007) studied this question. K149 mutations vs. Wild-type ClC-0 was evaluated on Voltage and chloride dependence of gating. Mutations at K149 in the ClC-0 chloride channel alter the voltage and chloride dependence of fast gating, likely due to electrostatic contributions to chloride binding.
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