Versatility of NaCl transport mechanisms in the cortical collecting duct

Abstract

The cortical collecting duct (CCD) forms part of the aldosterone-sensitive distal nephron and plays an essential role in maintaining the NaCl balance and acid-base status. The CCD epithelium comprises principal cells as well as different types of intercalated cells. Until recently, transcellular Na transport was thought to be restricted to principal cells, whereas (acid-secreting) type A and (bicarbonate-secreting) type B intercalated cells were associated with the regulation of acid-base homeostasis. This review describes how this traditional view has been upended by several discoveries in the past decade. A series of studies has shown that type B intercalated cells can mediate electroneutral NaCl reabsorption by a mechanism involving Na-dependent and Na-independent Cl/[Formula: see text] exchange, and that is energetically driven by basolateral vacuolar H-ATPase pumps. Other research indicates that type A intercalated cells can mediate NaCl secretion, through a bumetanide-sensitive pathway that is energized by apical H,K-ATPase type 2 pumps operating as Na/K exchangers. We also review recent findings on the contribution of the paracellular route to NaCl transport in the CCD. Last, we describe cross-talk processes, by which one CCD cell type impacts Na/Cl transport in another cell type. The mechanisms that have been identified to date demonstrate clearly the interdependence of NaCl and acid-base transport systems in the CCD. They also highlight the remarkable versatility of this nephron segment.

RETRACTED ARTICLE: Inhibition of inflammation using diacerein markedly improved renal function in endotoxemic acute kidney injured mice

“…Accumulating evidence has demonstrated that renal tubule function, including water reabsorption and urine concentration, is regulated by aquaporins (AQPs) and sodium transporters [ 4 – 6 ]. AQPs, a family of membrane proteins, play a critical role in regulating water balance [ 5 ].…”

“…Moreover, it has been shown that endotoxemia decreased AQP2 expression, which is responsible for the decrease of urine osmolality [ 2 ]. In addition, the major fraction of sodium is reabsorbed at the kidney proximal tubule by Na,K-ATPase, apical type 3 Na/H exchanger (NHE3) and Na-K-2Cl cotransporter (NKCC2) [ 6 ]. During endotoxemia, proximal tubular cells, the primary target of endotoxemia, develop abnormal expression or distribution of sodium transporters, leading to impaired sodium reabsorption [ 8 ].…”

A new variant of ASIC2 mediates sodium retention in nephrotic syndrome

“…These two pathways originate from principal cells and B-type intercalated cells respectively. In contrast, A-type intercalated can secrete sodium via basolateral Na/K/Cl co-transporter and apical H(Na),K-ATPase (Edwards & Crambert, 2017; Morla et al , 2016). Here we show that sodium reabsorption in CCD from CC-PAN rats is electrogenic and amiloride-sensitive but independent of any ENaC subunit, since none of them is expressed at the apical cell border (Lourdel et al , 2005), revealing the existence of a third pathway for sodium reabsorption.…”

The Fundamental Role of Bicarbonate Transporters and Associated Carbonic Anhydrase Enzymes in Maintaining Ion and pH Homeostasis in Non-Secretory Organs

“…The concentration of extracellular Cl − controls the body fluid content of ions, cellular volume, and blood pressure [68]. Likewise, Cl − plays a regulatory role in regulating HCO 3 − absorption and secretion [69] and activity of NBC [70]. NBCe1-B in its resting state is inhibited by high concentrations of intracellular Cl − ([Cl − ] i ) through the Cl − -interacting motif, GXXXP [70].…”