H+-K+-ATPases: regulation and role in pathophysiological states

Molecular cloning experiments have identified the existence of two H+-K+-AT Pases (HKAs), colonic and gastric. Recent functional and molecular studies indicate the presence of both transporters in the kidney, which are presume d to mediate the exchange of intracellular H+ for extracellular K+. On the basis of these studies, a picture is evolving that indicates differential r egulation of HKAs at the molecular level in acid-base and electrolyte disor ders. Of the two transporters, gastric HKA is expressed constitutively alon g the length of the collecting duct and is responsible for H+ secretion and K+ reabsorption under normal conditions and may be stimulated with acid-ba se perturbations and/or K+ depletion. This regulation may be species specif ic. To date there are no data to indicate that the colonic HKA (HKAc) plays a role in H+ secretion or K+ reabsorption under normal conditions. However , HKAc shows adaptive regulation in pathophysiological conditions such as K t depletion, NaCl deficiency, and proximal renal tubular acidosis, suggesti ng an important role for this exchanger in potassium, HCO3- and sodium (or chloride) reabsorption in disease states. The purpose of this review is to summarize recent functional and molecular studies on the regulation of HKAs in physiological and pathophysiological states. Possible signals responsib le far regulation of HKAs in these conditions will be discussed. Furthermor e, the role of these transporters in acid-base and electrolyte homeostasis will be evaluated in the context of genetically altered animals deficient i n HKAc.