Thick ascending limb: the Na+:K+:2Cl co-transporter, NKCC2, and the calcium-sensing receptor, CaSR

  • Gerardo GambaEmail author
  • Peter A. Friedman
Ion Channels, Receptors and Transporters


The thick ascending limb of Henle’s loop is a nephron segment that is vital to the formation of dilute and concentrated urine. This ability is accomplished by a consortium of functionally coupled proteins consisting of the apical Na+:K+:2Cl co-transporter, the K+ channel, and basolateral Cl channel that mediate electroneutral salt absorption. In thick ascending limbs, salt absorption is importantly regulated by the calcium-sensing receptor. Genetic or pharmacological disruption impairing the function of any of these proteins results in Bartter syndrome. The thick ascending limb is also an important site of Ca2+ and Mg2+ absorption. Calcium-sensing receptor activation inhibits cellular Ca2+ absorption induced by parathyroid hormone, as well as passive paracellular Ca2+ transport. The present review discusses these functions and their genetic and molecular regulation.


Diuretics Hypertension Salt transport Regulation Phosphorylation Isoforms 



Original studies described here were supported by grants DK 54171 and DK 64635 from the National Institutes of Health to PAF and GG, respectively, CONACYT grant 59992 to GG, and by a grant from the Foundation Leducq for the Transatlantic Network on Hypertension—Renal Salt Handling in the Control of Blood Pressure (GG).


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© Springer-Verlag 2008

Authors and Affiliations

  1. 1.Molecular Physiology UnitInstituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico CityMexico
  2. 2.Instituto de Investigaciones BiomédicasUniversidad Nacional Autónoma de MéxicoMexico CityMexico
  3. 3.Department of Pharmacology and Chemical BiologyUniversity of Pittsburgh School of MedicinePittsburghUSA

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