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| Content Provider | PubMed Central |
|---|---|
| Author | Sánchez-rodríguez, Jorge E. De, Santiago-castillo José A. Antonio, Contreras-vite Juan Nieto-delgado, Pablo G. Castro-chong, Alejandra Arreola, Jorge |
| Copyright Year | 2012 |
| Abstract | The interaction of either H+ or Cl− ions with the fast gate is the major source of voltage (V m) dependence in ClC Cl− channels. However, the mechanism by which these ions confer V m dependence to the ClC-2 Cl− channel remains unclear. By determining the V m dependence of normalized conductance (G norm(V m)), an index of open probability, ClC-2 gating was studied at different [H+]i, [H+]o and [Cl−]i. Changing [H+]i by five orders of magnitude whilst [Cl−]i/[Cl−]o = 140/140 or 10/140 mm slightly shifted G norm(V m) to negative V m without altering the onset kinetics; however, channel closing was slower at acidic pHi. A similar change in [H+]o with [Cl−]i/[Cl−]o = 140/140 mm enhanced G norm in a bell-shaped manner and shifted G norm(V m) curves to positive V m. Importantly, G norm was >0 with [H+]o = 10−10 m but channel closing was slower when [H+]o or [Cl−]i increased implying that ClC-2 was opened without protonation and that external H+ and/or internal Cl− ions stabilized the open conformation. The analysis of kinetics and steady-state properties at different [H+]o and [Cl−]i was carried out using a gating Scheme coupled to Cl− permeation. Unlike previous results showing V m-dependent protonation, our analysis revealed that fast gate protonation was V m and Cl− independent and the equilibrium constant for closed–open transition of unprotonated channels was facilitated by elevated [Cl−]i in a V m-dependent manner. Hence a V m dependence of pore occupancy by Cl− induces a conformational change in unprotonated closed channels, before the pore opens, and the open conformation is stabilized by Cl− occupancy and V m-independent protonation. |
| Related Links | http://dx.doi.org/10.1113/jphysiol.2012.232660 |
| Ending Page | 4253 |
| Page Count | 15 |
| Starting Page | 4239 |
| File Format | |
| ISSN | 00223751 |
| e-ISSN | 14697793 |
| Journal | The Journal of Physiology |
| Issue Number | Pt 17 |
| Volume Number | 590 |
| Language | English |
| Publisher | Blackwell Science Inc |
| Publisher Date | 2012-09-01 |
| Access Restriction | Open |
| Rights Holder | Blackwell Science Inc |
| Subject Keyword | Physiology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Physiology Sports Science |
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