The transport processes of Na+ in the second half of the proximal tubule are illustrated in Figure 34.3. Na+ and Cl− enter the cell through the apical membrane via parallel Na+/H+ (NHE3) and Cl−-base (such as formate, oxalate, and bicarbonate) antiporters (CFEX). Although multiple Cl−-base antiporters are involved, only one is depicted. The secreted H+ and base combine in the tubular fluid, forming an H-base complex that can recycle across the plasma membrane. The accumulation of the H-base complex in the tubular fluid establishes a concentration gradient, which facilitates H-base recycling into the cell across the apical plasma membrane. Inside the cell, H+ and the base dissociate and recycle back across the apical plasma membrane. Overall, this process leads to the uptake of NaCl across the apical membrane. The base can be hydroxide ions (OH−), formate (HCO2−), oxalate, HCO3−, or sulfate. The lumen of the tubular fluid possesses a positive transepithelial voltage generated by the diffusion of Cl− (from lumen to blood) across the tight junction. The high concentration of Cl− in the tubular fluid creates the driving force for Cl− diffusion. Additionally, some glucose is reabsorbed in the second half of the proximal tubule through a mechanism similar to that in the first half, except that the Na+/glucose symporter (SGLT1 gene) transports 2Na+ with one glucose and exhibits higher affinity and lower capacity compared to the Na+/glucose symporter in the first part of the proximal tubule (Figure 34.1). Glucose exits the cell via GLUT1 in the basolateral membrane instead of GLUT2, as seen in the first part of the proximal tubule. KCC refers to the KCl symporter. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) inhibit vasopressin (AVP)-stimulated water permeability. Na+ exits the cell via Na+,K+-ATPase, while Cl− leaves the cell and enters the blood through a K+/Cl− symporter (KCC) and a Cl− channel in the basolateral membrane.

In the second half of the proximal tubule, some NaCl is reabsorbed via a paracellular route. This occurs because the increase in Cl− concentration in the tubule fluid in the first half of the proximal tubule creates a concentration gradient (140 mEq/L in the tubule lumen and 105 mEq/L in the interstitium). The gradient promotes the diffusion of Cl− from the tubular lumen across the tight junctions into the lateral intercellular space. As a result, the movement of negatively charged Cl− causes the tubular fluid to become positively charged compared to blood. This positive transepithelial voltage drives the diffusion of positively charged Na+ out of the tubular fluid across the tight junction into the blood. Hence, in the second half of the proximal tubule, some Na+ and Cl− are reabsorbed passively across the tight junctions.

To summarize, the reabsorption of Na+ and Cl− in the proximal tubule occurs through both paracellular and transcellular pathways. Approximately 67% of the filtered NaCl is reabsorbed in the proximal tubule, with two-thirds of this amount moving through the transcellular pathway and the remaining one-third through the paracellular pathway (Table 34.4). The proximal tubule reabsorbs 67% of the filtered water.
•Fig. 34.3 Na+ transport processes in the second half of the proximal tubule. Na+ and Cl− enter the cell across the apical membrane through the operation of parallel Na+/H+ (NHE3) and Cl−-base (e.g., formate, oxalate, and bicarbonate) antiporters (CFEX). More than one Cl−-base antiporter is involved in this process, but only one is depicted. The secreted H+ and base combine in the tubular fluid to form an H-base complex that can recycle across the plasma membrane. Accumulation of the H-base complex in tubular fluid establishes a H-base concentration gradient that favors H-base recycling across the apical plasma membrane into the cell. Inside the cell, H+ and the base dissociate and recycle back across the apical plasma membrane. The net result is uptake of NaCl across the apical membrane. The base may be hydroxide ions (OH−), formate (HCO2−), oxalate, HCO3− , or sulfate. The positive transepithelial voltage in the lumen, indicated by the plus sign inside the circle in the tubular lumen, is generated by diffusion of Cl− (lumen to blood) across the tight junction. The high [Cl−] of tubular fluid provides the driving force for diffusion of Cl− . Some glucose is also reabsorbed in the second half of the proximal tubule by a mechanism similar to that described in the first half of the proximal tubule, except that the Na+/glucose symporter (SGLT1 gene) transports 2Na+ with one glucose and has higher affinity and lower capacity than the Na+/glucose symporter in the first part of the proximal tubule, depicted in
Fig. 34.1 . In addition, glucose exits the cell across the basolateral membrane via GLUT1 rather than via GLUT2 as in the first part of the proximal tubule (not shown). KCC, KCl symporter.
aAtrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) inhibit vasopressin (AVP)-stimulated water permeability.
and one or more Cl−-base antiporters (e.g., CFEX). Because the secreted H+ and base combine in the tubular fluid and reenter the cell, operation of the Na+/H+ and Cl−-base antiporters is equivalent to uptake of NaCl from tubular fluid into the cell. Na+ leaves the cell via Na+,K+-ATPase, and Cl− leaves the cell and enters the blood via a K+/ Cl− symporter (KCC) and a Cl− channel in the basolateral membrane.
Some NaCl is also reabsorbed across the second half of the proximal tubule via a paracellular route. Paracellular NaCl reabsorption occurs because the rise in [Cl−] in tubule fluid in the first half of the proximal tubule creates a [Cl−] gradient (140 mEq/L in the tubule lumen and 105 mEq/L in the interstitium). This concentration gradient favors diffusion of Cl− from the tubular lumen across the tight junctions into the lateral intercellular space. Movement of the negatively charged Cl− results in the tubular fluid becoming positively charged relative to blood. This positive transepithelial voltage causes diffusion of positively charged Na+ out of the tubular fluid across the tight junction into blood. Thus in the second half of the proximal tubule, some Na+ and Cl− are reabsorbed across the tight junctions via passive diffusion.
In summary, reabsorption of Na+ and Cl− in the proximal tubule occurs via both paracellular and transcellular pathways. Approximately 67% of the NaCl filtered each day is reabsorbed in the proximal tubule. Of this amount, two-thirds moves across the transcellular pathway, whereas the remaining one-third moves across the paracellular pathway (
Table 34.4
The proximal tubule reabsorbs 67% of the filtered water (