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Am J Physiol. 1984 Jun;246(6 Pt 2):F745-56.

Control of NaCl transport in the thick ascending limb.


The mammalian renal thick ascending limb of Henle serves to dilute the urine and supply energy for countercurrent multiplication as a consequence of its ability to absorb NaCl in excess of water. During the past few years our notions of the mechanism of and the factors that control NaCl absorption by the thick ascending limb of Henle have been altered substantially. This review presents evidence for a model of NaCl absorption in the thick ascending limb in which net Cl- absorption is rheogenic and involves a secondary active transport process. According to this model, net Cl- absorption occurs via a furosemide-sensitive coupled electroneutral (1Na+, 1K+, 2Cl-) apical Cl- entry mechanism in parallel with a large K+ conductance in apical plasma membranes and a conductive Cl- exit mechanism in basolateral plasma membranes. The lumen-positive voltage and high paracellular conductance in the thick ascending limb provides a means of driving 50% of net Na+ absorption through the paracellular route and reduces, with respect to exclusively transcellular active Na+ absorption, the metabolic energy expenditure for net Na+ absorption. In some mammalian species, ADH may enhance the rate of NaCl absorption in the medullary thick ascending limb by directly increasing the functional number of (1Na+, 1K+, 2Cl-) cotransport units as well as the K+ conductance unit in apical plasma membranes and by indirectly increasing basolateral membrane Cl- conductance. This latter effect on basolateral Cl- conductance may be secondary to a hormone-induced increase in cell Cl- activity. The ADH-dependent increase in NaCl absorption can be modified directly by both prostaglandin E2 and peritubular hypertonicity. During antidiuresis these hormonal and nonhormonal modulations of NaCl absorption may provide a number of feedback systems that control the level of interstitial osmolality and, as a consequence, concentrating power without affecting net NaCl absorption.

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