Acid-base transport systems in gastrointestinal epithelia.

Abstract

Cell plasma membranes contain a variety of transport systems that carry acid or base into or out of the cell. Research over the past decade has led to remarkable advances in our understanding of these acid-base transport systems and has established that they have several major physiological roles. They are the primary means by which cells regulate their internal pH and they also contribute importantly to regulation of cell volume and possibly cell proliferation. Furthermore, in the gastrointestinal tract they mediate absorption and secretion, not only of acids and bases but of several other electrolytes and nutrients. The major acid-base transport systems on mammalian cell plasma membranes are illustrated in Figures 1-3; their specific locations on different cell types are discussed later. Hydrogen, potassium (H+,K+) adenosine triphosphatase (ATPase) extrude H+ in exchange for K' using energy derived directly from ATP hydrolysis. They are present on the apical membranes of gastric parietal cells' (Fig 1) and, in some species, colon epithelial cells,2 where they mediate acid secretion. However, they are not widely distributed in gastrointestinal epithelia. Other acid base transport systems derive their energy, not directly from ATP hydrolysis, but from coupling the movement of one ion to passive movement of another ion along its electrochemical gradient. In the case of sodium/ hydrogen (Na+/H+) exchange (Figs 1-3), H' extrusion from the cell is coupled, in a 1: 1 ratio, to Na+ entry down its chemical gradient.3-' This gradient depends on the sodium pump, Na+,K+ ATPase, which is present on the basolateral membrane of all gastrointestinal epithelial cells and extrudes 3 Na+ ions in exchange for 2 K+ ions, thus maintaining a low intracellular [Na+], high intracellular [K'], and negative intracellular potential. Na+/H+ exchange is almost ubiquitous in mammalian cells and can be inhibited by the diuretic amiloride. There are several mechanisms for bicarbonate (HCO3 ) transport across plasma membranes.67 In most tissues, the enzyme carbonic anhydrase mediates rapid equilibration of H' and HCO3 with C02, which diffuses freely across all cell membranes. Therefore, HCO3 transport into the cell is equivalent to H` transport out of the cell and vice versa. In the case of chloride/bicarbonate (Cl-/ HC03 ) exchange (Figs 1-3), HCO3 extrusion from the cell is coupled, in a 1:1 ratio, to Cl entry along its chemical gradient. This gradirnt H+ HCO33Na+