Anion- and Proton-Dependent Gating of CIC-4 Anion/Proton Transporter under Uncoupling Conditions

作者：Orhan Goekce; Fahlke Christoph; Alekov Alexi K^*

来源：Biophysical Journal, 2011, 100(5): 1233-1241.

DOI：10.1016/j.bpj.2011.01.045

CIC-4 is a secondary active transporter that exchanges Cl(-) ions and H(+) with a 2:1 stoichiometry. In external SCN(-), CIC-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 CIC-4 by protons and anions to quantify association of substrates with the transporter. External acidification shifts voltage dependence of CIC-4 transport to more positive potentials and leads to reduced transport currents. Internal pH changes had less pronounced effects. Uncoupled CIC-4 transport is facilitated by elevated external [SCN(-)] but impaired by internal Cl(-) and l(-). Block by internal anions indicates the existence of an internal anion-binding site with high affinity that is not present in CIC channels. The voltage dependence of CIC-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 CIC channels and transporters.

• 出版日期2011-3-2