ClC-K Kidney Chloride Channels: From Structure to Pathology.

The molecular basis of chloride transport varies all along the nephron depending on the tubular segments especially in the apical entry of the cell. The major chloride exit pathway during reabsorption is provided by two kidney-specific ClC chloride channels ClC-Ka and ClC-Kb (encoded by CLCNKA and CLCNKB gene, respectively) corresponding to rodent ClC-K1 and ClC-K2 (encoded by Clcnk1 and Clcnk2). These channels function as dimers and their trafficking to the plasma membrane requires the ancillary protein Barttin (encoded by BSND gene). Genetic inactivating variants of the aforementioned genes lead to renal salt-losing nephropathies with or without deafness highlighting the crucial role of ClC-Ka, ClC-Kb, and Barttin in the renal and inner ear chloride handling. The purpose of this chapter is to summarize the latest knowledge on renal chloride structure peculiarity and to provide some insight on the functional expression on the segments of the nephrons and on the related pathological effects.