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Na + –K + –2Cl − cotransporter type 2 trafficking and activity: The role of interacting proteins
Author(s) -
Carmosino Monica,
Procino Giuseppe,
Svelto Maria
Publication year - 2012
Publication title -
biology of the cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 85
eISSN - 1768-322X
pISSN - 0248-4900
DOI - 10.1111/boc.201100049
Subject(s) - cotransporter , reabsorption , loop of henle , symporter , biology , downregulation and upregulation , endocrinology , phenotype , pathogenesis , medicine , transporter , microbiology and biotechnology , gene , kidney , genetics , chemistry , immunology , sodium , organic chemistry
The central role of Na + –K + –2Cl − cotransporter type 2 (NKCC2) in vectorial transepithelial salt reabsorption in thick ascending limb cells from Henle's loop in the kidney is evidenced by the effects of loop diuretics, the pharmacological inhibitors of NKCC2, that are amongst the most powerful antihypertensive drugs available to date. Moreover, genetic mutations of the NKCC2 encoding gene resulting in impaired apical targeting and function of NKCC2 transporter give rise to a pathological phenotype known as type I Bartter syndrome, characterised by a severe volume depletion, hypokalaemia and metabolic alkalosis with high prenatal mortality. On the contrary, excessive NKCC2 activity has been linked with inherited hypertension in humans and in rodent models. Interestingly, in animal models of hypertension, NKCC2 upregulation is achieved by post‐translational mechanisms underlining the need to analyse the molecular mechanisms involved in the regulation of NKCC2 trafficking and activity to gain insights in the pathogenesis of hypertension.