SLC12A1 antibody

Background of SLC12A1 antibody

Electrically silent Na(+)-(K+)-Cl- transporter systems are present in a wide variety of cells and serve diverse physiological functions. In chloride secretory and absorbing epithelia, these cotransporters provide the chloride entry mechanism crucial for trans-cellular chloride transport. Renal handling of NaCl is a major determinant for homeostasis of salt and extracellular fluid volumes and consequently blood pressure. The kidney specific Na-K-co-transporter (NKCC2) facilitates and mediates the transport of Na and Cl across the luminal membrane of the thick ascending limb of the loop of Henle and the macula densa. NKCC2 mutations and lack of function caused Bartters syndrome and led to salt-wasting in neonates (1). Diuretics like bumetimide, furosemide act on NKCC2. A second physiological function of KCC2 is its involvement in tubuloglomerular feedback to control the renal blood flow. The renal-specific NKCC2 (Na+–K+–2Cl− co-transporter 2) is regulated by changes in phosphorylation state by metabolic sensing kinase (AMPK) which phosphorylates the serine126 (1). The chloride-sensitive activation of NKCC2 requires the interaction of two serine-threonine kinases, WNK3 and SPAK. WNK3 is positioned upstream of SPAK and appears to be the chloride-sensitive kinase. Elimination of WNK3’s unique SPAK-binding motif prevents its activation of NKCC2, as does the mutation of thr 96, 101, and 111 (2). The expression of NKCC2 in the thick ascending loop of Henle is decreased by cGMP mediated by PDE2A (3).
The two major electroneutral sodium-chloride transporters present in the mammalian kidney, the bumetanide-sensitive Na(+)-K(+)-Cl- symporter and thiazide-sensitive Na(+)-Cl- cotransporter, and have characterized. Despite their differing sensitivities to bumetanide and thiazides and their different requirements for potassium, these approximately 115-kDa proteins share significant sequence similarity (approximately 60%) and exhibit a topology featuring 12 potential membrane-spanning helices flanked by long non-hydrophobic domains at the NH2 and COOH termini. The NKCC2 has an apparent molecular weight of around 160kDa in ascending loop of Henle (4).