The paracellular pathway plays a significant role in the transport of solute and water across epithelia, depending on the type of epithelium. The specific claudins expressed by the cell determine the permeability characteristics of the tight junction, which can vary from low permeability to high permeability for solutes, water, or both. Epithelia with high rates of transepithelial transport generally have leaky tight junctions, such as the proximal tubule of the renal nephron and the early segments of the small intestine. On the other hand, epithelia that establish large transepithelial gradients for solutes, water, or both typically have tight tight junctions, like the collecting duct of the renal nephron, the urinary bladder, and the terminal portion of the colon. The tight junction may also be selective for certain solutes.

All solute transport through the paracellular pathway is passive and driven by the transepithelial concentration gradient and the transepithelial voltage, especially for charged solutes. The transepithelial voltage can be oriented with the apical surface electrically negative in relation to the basolateral surface or electrically positive. Its polarity and magnitude are determined by the membrane transporters in the apical and basolateral membranes, as well as the tight junction's permeability characteristics.

It is important to note that transcellular transport processes establish the transepithelial chemical and voltage gradients, which then drive paracellular transport. This is exemplified in the reabsorption and secretion of NaCl in different epithelia. The transepithelial voltage is electrically negative on the apical surface compared to the basolateral surface in both cases. In the NaCl-reabsorbing epithelium, the active transcellular reabsorption of Na+ generates the transepithelial voltage, leading to Cl- reabsorption through the paracellular pathway. Conversely, in the NaCl-secreting epithelium, the active transcellular secretion of Cl- generates the transepithelial voltage, causing passive secretion of Na+ through the paracellular pathway.

Water movement across epithelia is passive and driven by transepithelial osmotic pressure gradients. It can occur via the transcellular route involving aquaporins in both the apical and basolateral membranes, as well as through the paracellular pathway. The described processes can be observed in the NaCl-reabsorbing epithelium.
Depending on the epithelium, the paracellular pathway is an important route for transepithelial transport of solute and water. As noted, the permeability characteristics of the paracellular pathway are determined, in large part, by the specific claudins that are expressed by the cell. Thus the tight junction can have low permeability for solutes, water, or both, or it can have a high permeability. For epithelia in which there are high rates of transepithelial transport, •Fig. 2.12 The Electrical Profile Across an Epithelial Cell. Themagnitudeofthemembranevoltages,andthetransepithelialvoltagearedeterminedbythevariousmembranetransportproteinsintheapicalandbasolateralmembranes.Thetransepithelialvoltageisequaltothesumoftheapicalandbasolateralmembranevoltages(seetextfordetails).
the tight junctions typically have a high permeability (i.e., are leaky). Examples of such epithelia include the proximal tubule of the renal nephron and the early segments of the small intestine (e.g., duodenum and jejunum). If the epithelium must establish large transepithelial gradients for solutes, water, or both, the tight junctions typically have low permeability (i.e., are tight). Examples of this type of epithelium include the collecting duct of the renal nephron, the urinary bladder, and the terminal portion of the colon. In addition, the tight junction may be selective for certain solutes (e.g., cation versus anion selective).
All solute transport that occurs through the paracellular pathway is passive in nature. The two driving forces for this transport are the transepithelial concentration gradient for the solute and, if the solute is charged, the transepithelial voltage (Fig. 2.12 ). The transepithelial voltage may be oriented with the apical surface electrically negative in relation to the basolateral surface as shown in
Fig. 2.12 , or it may be oriented with the apical surface electrically positive in relation to the basolateral surface. The polarity and magnitude of the transepithelial voltage is determined by the specific membrane transporters in the apical and basolateral membranes, as well as by the permeability characteristics of the tight junction.
It is important to recognize that transcellular transport processes set up the transepithelial chemical and voltage gradients, which in turn can drive paracellular transport. This is illustrated in
Fig. 2.13 for an epithelium that reabsorbs NaCl and for an epithelium that secretes NaCl. In both epithelia, the transepithelial voltage is oriented with the apical surface electrically negative in relation to the basolateral surface. For the NaCl-reabsorbing epithelium, the transepithelial voltage is generated by the active, transcellular reabsorption of Na+ . This voltage in turn drives Cl− reabsorption through the paracellular pathway. In contrast, for the NaCl-secreting epithelium, the transepithelial voltage is generated by the active transcellular secretion of Cl− . Na+ is then secreted passively via the paracellular pathway, driven by the negative transepithelial voltage.
Water movement across epithelia is passive and driven by transepithelial osmotic pressure gradients. Water movement can occur by a transcellular route involving aquaporins in both the apical and basolateral membranes.
In addition, water may also move through the paracellular pathway. In the NaCl-reabsorbing epithelium depicted in