Bicarbonate transport along the loop of Henle: molecular mechanisms and regulation.
The loop of Henle (LOH) is an important site of renal tubule acidification. A combination of several techniques, including in vivo microperfusion, perfusion in vitro of the S3 segment of the proximal tubule and of the thick ascending limb (TAL) of Henle's loop, as well as quantitative PCR performed on isolated TAL, has permitted the definition of key transporters and their role in modulating bicarbonate reabsorption in physiological and pathophysiological conditions. Na(+)-H+ exchange is the most important transport mechanism responsible for bicarbonate reabsorption, although a small but significant contribution of H(+)-ATPase-mediated bicarbonate reabsorption can also be identified. NHE3 is the main of several NHE isoforms expressed in the TAL and in the S3 segment of the proximal tubule. Special properties of the Na(+)-H+ exchanger in the TAL are its relative insensitivity to changes in cell pH (pHi) and the tight coupling between apical and basolateral Na(+)-H+ exchange. Several hormones, including anti-diuretic hormone (ADH), angiotensin II (AII), and gluco- and mineralocorticoids regulate Na(+)-H+ exchange. Loop diuretics such as furosemide stimulate bicarbonate transport along the LOH. Systemic acid-base disturbances also modulate bicarbonate transport: acidosis increases bicarbonate reabsorption, while metabolic alkalosis has the opposite effect. Neither hypokalemic alkalosis nor respiratory alkalosis or respiratory acidosis alter bicarbonate transport along the LOH. A significant role of HCO3 backflux, most likely through the paracellular pathway of the TAL, can also be observed. Changes in extracellular osmolality also affect bicarbonate reabsorption: hypertonicity inhibits, whereas hypotonicity stimulates transport. Transport activation is also observed as an adaptive response to glomerular hyperfiltration.
Capasso
Giovambattista
G
Chair of Nephrology, Research Center for Cardiovascular Diseases, School of Medicine, Second University of Naples, Italy. gb.capasso@unina2.it
Unwin
Robert
R
Rizzo
Maria
M
Pica
Angelo
A
Giebisch
Gerhard
G
D000042:Absorption / Q000502:physiology; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D001692:Biological Transport / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D008138:Loop of Henle / Q000378:metabolism*; D006180:Proton-Translocating ATPases / Q000502:physiology; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology
D001639:Bicarbonates; D017923:Sodium-Hydrogen Exchangers; D006180:Proton-Translocating ATPases