Concentration and pH dependence of skeletal muscle chloride channel ClC-1

Item Type:	Article
Title:	Concentration and pH dependence of skeletal muscle chloride channel ClC-1
Creators Name:	Rychkov, G.Y. and Pusch, M. and Astill, D.S. and Roberts, M.L. and Jentsch, T.J. and Bretag, A.H.
Abstract:	1. The influence of Cl- concentration and pH on gating of the skeletal muscle Cl- channel, ClC-1, has been assessed using the voltage-clamp technique and the Sf-9 insect cell and Xenopus oocyte expression systems. 2. Hyperpolarization induces deactivating inward currents comprising a steady-state component and two exponentially decaying components, of which the faster is weakly voltage dependent and the slower strongly voltage dependent. 3. Open probability (Po) and kinetics depend on external but not internal Cl- concentration. 4. A point mutation, K585E, in human ClC-1, equivalent to a previously described mutation in the Torpedo electroplaque chloride channel, ClC-0, alters the I-V relationship and kinetics, but retains external Cl- dependence. 5. When external pH is reduced, the deactivating inward currents of ClC-1 are diminished without change in time constants while the steady-state component is enhanced. 6. In contrast, reduced internal pH slows deactivating current kinetics as its most immediately obvious action and the Po curve is shifted in the hyperpolarizing direction. Addition of internal benzoate at low internal pH counteracts both these effects. 7. A current activated by hyperpolarization can be revealed at an external pH of 5.5 in ClC-1, which in some ways resembles currents due to the slow gates of ClC-0. 8. Gating appears to be controlled by a Cl(-)-binding site accessible only from the exterior and, possibly, by modification of this site by external protonation. Intracellular hydroxyl ions strongly affect gating either allosterically or by direct binding and blocking of the pore, an action mimicked by intracellular benzoate.
Keywords:	Benzoates, Benzoic Acid, Chloride Channels, Chlorides, Drug Dose-Response Relationship, Food Preservatives, Hydrogen-Ion Concentration, Ion Channel Gating, Kinetics, Membrane Potentials, Skeletal Muscle, Mutation, Oocytes, Patch-Clamp Techniques, Animals, Rats, Xenopus
Source:	Journal of Physiology
ISSN:	0022-3751
Publisher:	Cambridge University Press
Volume:	497
Number:	Pt 2
Page Range:	423-435
Date:	1 December 1996
Official Publication:	http://jp.physoc.org/content/497/Pt_2/423.abstract
PubMed:	View item in PubMed

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