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

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.