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• W1970307974 startingPage "633" @default.
• W1970307974 abstract "The volume-sensitive chloride current (IClVol) exhibit a time-dependent decay presumably due to channel inactivation. In this work, we studied the effects of chloride ions (Cl−) and H+ ions on IClVol decay recorded in HEK-293 and HL-60 cells using the whole-cell patch clamp technique. Under control conditions ([Cl−]e = [Cl−]i = 140 mM and pHi = pHe = 7.3), IClVol in HEK cells shows a large decay at positive voltages but in HL-60 cells IClVol remained constant independently of time. In HEK-293 cells, simultaneously raising the [Cl−]e and [Cl−]i from 25 to 140 mM (with pHe = pHi = 7.3) increased the fraction of inactivated channels (FIC). This effect was reproduced by elevating [Cl−]i while keeping the [Cl−]e constant. Furthermore, a decrease in pHe from 7.3 to 5.5 accelerated current decay and increased FIC when [Cl−] was 140 mM but not 25 mM. In HL-60 cells, a slight IClVol decay was seen when the pHe was reduced from 7.3 to 5.5. Our data show that inactivation of IClVol can be controlled by changing either the Cl− or H+ concentration or both. Based on our results and previously published data, we have built a model that explains VRAC inactivation. In the model the H+ binding site is located outside the electrical field near the extracellular entry whilst the Cl− binding site is intracellular. The model depicts inactivation as a pore constriction that happens by simultaneous binding of H+ and Cl− ions to the channel followed by a voltage-dependent conformational change that ultimately causes inactivation." @default.
• W1970307974 created "2016-06-24" @default.
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• W1970307974 date "2010-05-09" @default.
• W1970307974 modified "2023-10-18" @default.
• W1970307974 title "Control of volume-sensitive chloride channel inactivation by the coupled action of intracellular chloride and extracellular protons" @default.
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• W1970307974 doi "https://doi.org/10.1007/s00424-010-0842-0" @default.
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