The Journal of General Physiology
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Published 27 June 2001. doi:10.1085/jgp.118.1.23
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© The Rockefeller University Press, 0022-1295/2001/7/23/ $5.00
The Journal of General Physiology, Volume 118, Number 1, July 1, 2001 23-32


Original Article

Different Fast-gate Regulation by External Cl- and H+ of the Muscle-type ClC Chloride Channels

Mei-Fang Chena and Tsung-Yu Chena,b
a Center for Neuroscience, University of California, Davis, CA 95616
b Department of Neurology, University of California, Davis, CA 95616

Correspondence to: Tsung-Yu Chen, Center for Neuroscience, University of California, 1544 Newton Court, Davis, California 95616. Fax:(530)757-8827 E-mail:tycchen{at}ucdavis.edu.

The fast gate of the muscle-type ClC channels (ClC-0 and ClC-1) opens in response to the change of membrane potential (V). This gating process is intimately associated with the binding of external Cl- to the channel pore in a way that the occupancy of Cl- on the binding site increases the channel's open probability (Po). External H+ also enhances the fast-gate opening in these channels, prompting a hypothesis that protonation of the binding site may increase the Cl- binding affinity, and this is possibly the underlying mechanism for the H+ modulation. However, Cl- and H+, modulate the fast-gate Po-V curve in different ways. Varying the external Cl- concentrations ([Cl-]o) shifts the Po-V curve in parallel along the voltage axis, whereas reducing external pH mainly increases the minimal Po of the curve. Furthermore, H+ modulations at saturating and nonsaturating [Cl-]o are similar. Thus, the H+ effect on the fast gating appears not to be a consequence of an increase in the Cl- binding affinity. We previously found that a hyperpolarization-favored opening process is important to determine the fast-gate Po of ClC-0 at very negative voltages. This [Cl-]o-independent mechanism attracted little attention, but it appears to be the opening process that is modulated by external H+.

Key Words: channel gating, ClC-0, ClC-1, pH regulation, Cl- dependence


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