Date: 04 Nov 2008

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

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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.

This review is dedicated to the memory of Dr. Steven C. Hebert. Dr. Hebert, our colleague and friend, was a leader in elucidating the mechanism and regulation of salt and water balance by the kidney. He embodied the foresight to anticipate many of the elements contributing to renal homeostasis, an infectious enthusiasm that inspired fellows and colleagues alike, and an open and welcoming collegiality that represents all the best traits of academia.