Referenced in: none

Automatically associated channels: ClC4

Title: Anion- and Proton-Dependent Gating of ClC-4 Anion/Proton Transporter under Uncoupling Conditions.

Authors: Gökce Orhan, Christoph Fahlke, Alexi K Alekov

Journal, date & volume: Biophys. J., 2011 Mar 2 , 100, 1233-41

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21354396

Abstract
ClC-4 is a secondary active transporter that exchanges Cl(-) ions and H(+) with a 2:1 stoichiometry. In external SCN(-), ClC-4 becomes uncoupled and transports anions with high unitary transport rate. Upon voltage steps, the number of active transporters varies in a time-dependent manner, resembling voltage-dependent gating of ion channels. We here investigated modification of the voltage dependence of uncoupled ClC-4 by protons and anions to quantify association of substrates with the transporter. External acidification shifts voltage dependence of ClC-4 transport to more positive potentials and leads to reduced transport currents. Internal pH changes had less pronounced effects. Uncoupled ClC-4 transport is facilitated by elevated external [SCN(-)] but impaired by internal Cl(-) and I(-). Block by internal anions indicates the existence of an internal anion-binding site with high affinity that is not present in ClC channels. The voltage dependence of ClC-4 coupled transport is modulated by external protons and internal Cl(-) in a manner similar to what is observed under uncoupling conditions. Our data illustrate functional differences but also similarities between ClC channels and transporters.