Na+/Cl- cotransport Na+, K+/2Cl- cotransport K+/Cl- cotransport PathwayStep4875 PathwayStep4874 PathwayStep4873 Cation-coupled Chloride cotransporters Authored: Jassal, B, 2009-06-12 Edited: Jassal, B, 2009-06-12 Pubmed12739168 Pubmed15788703 Reactome Database ID Release 43426117 Reactome, http://www.reactome.org ReactomeREACT_19315 Reviewed: He, L, 2009-08-24 The cation-chloride cotransporter family (SLC12 gene family) are membrane proteins that cotranslocate chloride (Cl-) with either Na+, K+, or both cations electroneutrally. The general topology of these proteins feature 12 transmembrane domains flanked by hydrophilic NH2 and COOH-terminal domains. They are secondary transporters and movement of these cations is determined by gradients established by primary transporters such as Na+-K+-ATPase. Cotransporters that use Na+ as the driving force move Cl- into the cell because Na+ concentration is higher in the extracellular region. Conversely, cotransporters that use K+ as the driving force move Cl- out of the cell because K+ concentration is higher inside the cell.<br><br>The SLC12 gene family contains nine members, of which seven are clearly characterized genes and two are orphans. They encode cotransporter proteins which are 1) involved in Cl- homeostasis, 2) regulate cell volume, 3) involved in transepithelial ion movement (salt reabsorption in the kidney) and 4) involved in response to neurotransmitters such as GABA. <br><br>Three different cotransporter subtypes are expressed by the seven characterized genes; one thiazide-sensitive Na+/Cl- cotransporter, two loop diuretic-sensitive Na+, K+/2Cl- cotransporters and four K+/Cl- cotransporters (Gamba G, 2005; Hebert SC et al, 2004).