Proximal Tubule Transport

  • The proximal tubule is the major resorptive segment of the nephron and accounts for resorption of nearly two-thirds of all filtered water, sodium, and chloride. In addition, the proximal tubule is the segment where the majority of critical organic solutes such as glucose and amino acids are resorbed. Finally, this segment also plays an important role in acid-base balance as it is involved in bicarbonate resorption and secretion of organic acids.

Molecular mechanisms of proximal tubule transport
Transport in the proximal tubule is slightly different in the early and late portions of this segment. Early on, sodium is resorbed together with phosphate or organic solutes such as amino acids, glucose, and citrate on a variety of solute-specific symporters (represented by a single generic symporter in this figure). The early proximal tubule is largely impermeable to chloride which builds up in concentration. Paracellular chloride permeability substantially increases in the late proximal tubule and the large electrochemical gradient for chloride generated in the early tubule is released through large amounts of chloride resorption in the late portion. The positive luminal charge thus created by the loss of negative ions enhances paracellular sodium resorption in the late segment. Nearly all transport in the proximal tubule is powered by a basolateral Na-K ATPase. In addition to the mechanisms described, sodium is resorbed in exchange for hydrogen ions via Na-H antiporters throughout the entire proximal tubule. Secretion of acid in the proximal tubule is a critical aspect of bicarbonate resorption which also occurs in this segment but is not pictured here as it is discussed under the bicarbonate excretion section.

Transport Mechanisms
  • Overview
    • The enormous resorptive capacity of the proximal tubule is largely powered by a basolateral NaK ATPase which generates low Na+ concentrations within the tubular epithelial cells. This low intracellular Na+ concentration is then used to actuate resorption not only of tubular sodium but also other solutes and water as described below. To support the enormous energy required to continuously power the basolateral NaK ATPase tubular epithelial cells of the proximal tubule display prominent mitochondria. Furthermore, the apical membrane possesses a brush border which substantially increases this segments resorptive surface area.
  • Sodium Resorption
    • As mentioned, sodium resorption in the proximal tubule is largely actuated through primary active transport via a basolateral NaK ATPase which generates a strong electrochemical gradient for sodium resorption across the nephronic barrier. Tubular sodium then undergoes transcellar transport through the luminal membrane via a variety of porters. Some of these porters are symporters which link transport of sodium with distinct organic molecules such as glucose and amino acids. However, the largest contribution is likely made by NaH Antiporters which link secretion of hydrogen with resorption of sodium. These transcellular transport processes appear to be most important in the early proximal tubule whereas in the late proximal tubule sodium appears to be transported via a paracellular route across tubular epithelial cell tight junctionss. In this paracellular context, sodium resorption occurs with that of chloride, as described below.
  • Organic Solutes and Phosphate
    • Organic solutes such as glucose and amino acids as well as phosphate are resorbed via specific symporters that molecularly link sodium resorption with that of the solute. Because resorption of organic solutes and phosphate is powered by the sodium electrochemical gradient, their transport is considered to occur through secondary active transport. Once inside the tubular epithelial cells, these organic solutes or phosphate cross the basolateral membrane via specific membrane porters as they run down their concentration gradients into the interstitial fluid.
  • Water
    • The tight junctions of the proximal tubule are highly permeable to water and thus water resorption follows that of other solutes, especially sodium, via osmosis. It is important to point out that because water is resorbed with sodium, the effective concentration of sodium within the tubular fluid does not decline even though large amounts of both molecules are resorbed.
  • Chloride
    • Chloride ions are largely not transported in the early proximal tubule and thus the luminal chloride concentration increases as water is resorbed. By the late proximal tubule, the chloride concentration is relatively high compared to the renal interstitial fluid, generating a strong electrochemical gradient for chloride resorption. Consequently, in the late proximal tubule, a substantial amount of chloride is resorbed paracellularly through permeable tight junctions. This rapid loss of negative charge generates a net positive potential within the tubular fluid which may be responsible for the paracellular sodium resorption that occurs in the late proximal tubule.
  • Bicarbonate
  • Calcium
    • As discussed in regulation of calcium excretion, the proximal tubule is responsible for resorbing roughly 67% of the filtered calcium. Calcium resorption in this segment occurs largely via a paracellular pathway and appears to be dependent on the resorption of sodium.