Fig. 34.8 ). Na+ leaves the cell via the action of Na+,K+-ATPase, and Cl− leaves the cell via diffusion through Cl− channels and a K+/Cl− symporter (KCC4). Thus dilution of tubular fluid begins in the thick ascending limb and continues in the early segment of the distal tubule.
The last segment of the distal tubule (late distal tubule) and the collecting duct are composed of three cell types: principal cells and two types of intercalated cells. As illustrated in
Fig. 34.9, principal cells reabsorb NaCl and water and secrete K+ . Both Na+ reabsorption and K+ secretion by these cells depend on the activity of Na+,K+-ATPase in the basolateral membrane. By maintaining a low intracellular [Na+], the Na+,K+-ATPase provides a favorable chemical gradient for movement of Na+ from tubular fluid into the cell. Because Na+ enters the cell across the apical membrane via diffusion through epithelial Na+-selective channels (ENaCs), the negative voltage inside the cell facilitates entry of Na+, which then exits the cell and enters the blood via the basolateral membrane Na+,K+-ATPase. Reabsorption of Na+ generates a negative luminal voltage across the late distal tubule and collecting duct, which provides the driving force for paracellular reabsorption of Cl− . Intercalated cells secrete either H+ or HCO3 − and play important roles in acid-base homeostasis (see ). The α-intercalated cell (see
Fig. 34.9 , center) secretes H+ and reabsorbs both HCO3 − and K+ and is thus important in regulating acid-base balance (see ). α-Intercalated cells reabsorb K+ by the operation of an H+,K+-ATPase (HKA) located in the apical plasma membrane. In contrast, β-intercalated cells (see
Fig. 34.9 , bottom) secrete HCO3 − and reabsorb both H+ and Cl− . Chloride enters the β-intercalated cell across the apical membrane via a Cl−/HCO3 − antiporter (pendrin) and leaves the cell across the basolateral membrane via a Cl− channel. A variable amount of water is reabsorbed across principal cells in the late distal tubule and collecting duct. Water reabsorption in these segments is mediated by the AVP-regulated AQP2 water channel located in the apical plasma membrane and by AQP3 and AQP4 located in the basolateral membrane of principal cells. In the presence of water (see
K+ is secreted from blood into tubular fluid by principal cells in two steps (see
Fig. 34.9, top).
First, uptake of K+ across the basolateral membrane is mediated by the action of Na+,K+-ATPase. Second, K+ leaves the cell via passive diffusion. Because [K+] inside principal cells is high (≈150 mEq/L) and [K+] in tubular fluid is low (≈10 mEq/L), K+ diffuses down its concentration gradient through apical cell membrane K+ channels (ROMK and BK) into tubular fluid. Although the negative potential inside these cells favors intracellular K+ retention, the electrochemical gradient across the apical membrane promotes secretion of K+ from the cell into tubular fluid (see ). In contrast, K+ reabsorption by α cells is mediated by an H+,K+-ATPase (HKA) located in the apical cell membrane (see
Fig. 34.9 , center). As a consequence these distal nephron segments possess the ability to both secrete and reabsorb K+ via independently regulated mechanisms, which contrasts with the general tendency to reabsorb Na+ along most nephron segments.
Regulation of NaCl and Water Reabsorption
Quantitatively, angiotensin II, aldosterone, catecholamines, natriuretic peptides, and uroguanylin are the most important hormones regulating NaCl reabsorption and thereby urinary NaCl excretion (