Chloride Channels (CLC1-7, CLC-K1/K2) Antibodies

Chloride is a critical component of all living cells. It is also the single most dominant diffusible anion inside of most cells - the others are mostly impermeable organic anions. Since cytoplasmic electroneutrality is maintained under normal physiological environment, changes in cellular chloride level is accompanied by total cell solute content. Because of high water permeability of cell membranes, changes in cell solute content are accompanied by changes in cellular volume. Voltage-gated chloride channels regulate cellular traffic of chloride ion. The chloride channels (CIC or CLC) perform several functions including the regulation of cell volume, membrane potential stabilization, signal transduction, and transepithelial transport. Mutations in CIC genes have been linked with several human diseases including myotonias (Thomsen's disease), cystic fibrosis, Bartters syndrome type III, Dent's disease, and X-linked recessive nephrolithiasis.
Since the cloning of first member of CLC from Torpedo electric organ (CLC-0), many mammalian homolgs have been identified. In mammals, CLC proteins form a superfamily of at least 9 different genes (CLC1-7 also known as CLCN1-7 and CLK1-2 or CLCKa and CLCKb). Additional forms of these proteins are obtained by alternative splicing. A detailed sequence comparison of CLC has revealed three closely related groups: One group contains CLC-1, CLC-2, and the renal CLC-K1 and CLC-K2; a Second group comprises of CLC-3, CLC-4, and CLC-5; The third group has CLC-6 and CLC-7. All CLC proteins (~700-1000 aa) are predicted to contain 10 (possibly 12) transmembrane domains with intracellular N and C-termini. Except CLC-1 and CLC-K1/K2 that are specific for kidney, most other CLC are widely distributed in various tissues.
CLC-1 has been linked with myotonia congenita, an unusual syndrome associated w ith muscular stiffness caused by delayed relaxation of muscle following voluntary contractions. Bartter's syndrome, a rare disorder associated with renal salt wasting and hypokalemic alkalosis, has mutation in CLC-K2. Mutations or deletions in CLC-5 have been linked with Dent's diseases (excessive urinary calcium, urinary low mol wt proteinuria, and calcium kidney stone), and four related X-linked syndromes of hypercalciuric nephrolithiasis.
ADI has produced highly specific rabbit antibodies to CLC1-7, and CLC-K1/K2 using peptide sequences specific to each CLCs. These antibodies should be useful in studying various CLCs.