ABSTRACT
ClC-type chloride channel proteins are widely distributed throughout the biological cell membrane, and functionally divided into two types of categories: passive Cl channels and secondary active Cl/H+ transporters (Accardi & Picollo 2010, Jentsch 2008, Miller 2006). In the passive Cl channels, the selective chloride ions flow down its electrochemical gradient. The transporters, which are also known as Cl/H+ exchangers or antiporters, couple a fixed stoichiometric exchange of chloride ions and protons in the opposite direction (Accardi & Miller, 2004). Although they have dierent functions, similar molecular architectures existed among them (Dutzler, 2007, Feng et al., 2010). In the human genome, there are nine ClC members which are strictly divided functional properties. Among them, four ClC proteins (ClC-1, ClC-2, ClC-Ka, and ClC-Kb) are divided as ion channels and the other five ClCs (ClC 3-7) are considered as transporters (Jentsch et al., 2005, Achcroft et al., 2009, Jentsch, 2008). These proteins play critical functional roles such as, regulating the membrane action potential, muscle excitability, renal intravascular transport, cell flexibility, and so on (Accardi & Picollo, 2010, Miller, 2006, Jentsch, 2008). Several genetic diseases in humans are directly associated with functionally defection of ClC mutants (Chen, 2005, Lourdel et al., 2012).
