AFLUID June 45/6

Silver, Randi B., and Manoocher Soleimani. H1-K1-ATPases: regulation and role in pathophysiological states. Am. J. Physiol. 276 (Renal Physiol. 45): F799–F811, 1999.—Molecular cloning experiments have identified the existence of two H1-K1-ATPases (HKAs), colonic and gastric. Recent functional and molecular studies indicate the presence of both transporters in the kidney, which are presumed to mediate the exchange of intracellular H1 for extracellular K1. On the basis of these studies, a picture is evolving that indicates differential regulation of HKAs at the molecular level in acid-base and electrolyte disorders. Of the two transporters, gastric HKA is expressed constitutively along the length of the collecting duct and is responsible for H1 secretion and K1 reabsorption under normal conditions and may be stimulated with acid-base perturbations and/or K1 depletion. This regulation may be species specific. To date there are no data to indicate that the colonic HKA (HKAc) plays a role in H1 secretion or K1 reabsorption under normal conditions. However, HKAc shows adaptive regulation in pathophysiological conditions such as K1 depletion, NaCl deficiency, and proximal renal tubular acidosis, suggesting 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 responsible for regulation of HKAs in these conditions will be discussed. Furthermore, the role of these transporters in acid-base and electrolyte homeostasis will be evaluated in the context of genetically altered animals deficient in HKAc.