Functional and structural studies demonstrate that Cl^– channels of the ClC family have a dimeric double-barrelled structure, with each monomer contributing an identical pore. We have recently provided evidence for the presence of slow and fast hyperpolarisation-dependent gating processes in ClC-2 that might correspond to protopore gating and common process opening both pores simultaneously. Unlike the case with ClC-0, the prototype ClC Cl^– channel, the two gating processes in ClC-2 are not independent (Niemeyer et al., 2003;Zuñiga et al., 2004). Recently the role of C-terminus CBS domains in the common gating process of ClC-0 and ClC-1 has been demonstrated (Estevez et al., 2004), with a single-point mutation abolishing this gate. There is a high degree of conservation of CBS domains in ClC-2 and we have now examined the effect of the mutating the corresponding amino acid (H811) on ClC-2 gating. We have used the recombinant guinea pig ClC-2 transiently expressed in HEK-293 cells and assayed by the whole-cell recording mode of the patch-clamp technique. The H811A mutant of ClC-2 is seen to conserve the strict inward rectification of the WT channel, but with a much faster kinetics for opening and closing. The overall kinetics is still bi-exponential but the time constants are decreased two-fold in the mutant. The voltage-dependence of H811A is shifted to more positive potentials by about 30 mV. Cd²⁺ is known to block ClC channels purportedly by facilitating slow closing. However, Cd²⁺ inhibited to same extent and affinity both WT and H811A channels. Interestingly the intracellular Cl^– dependence is not affected by the mutation. V_0.5is related linearly to log[Cl^– ]_i with similar slope in H811A and WT channels. Neutralisation of a conserved pore glutamic acid residue (E217) has been shown to abolish all Cl^–_i dependence in ClC-2 (Niemeyer et al., 2003). This mutant retains, however, a residual voltage-dependence that has been attributed to slow, common gate. The double mutant E217V-H811A is a constitutive open channel completely lacking any gating. We conclude that, if ClC-2 has both fast and slow gating processes, akin to the protopore and common gates of other ClC channels, these two processes must be highly coupled.