The nongastric H+-K+-ATPases: molecular and functional properties

The Na-WH-K-ATPase gene family is divided in three subgroups including the Na-K-ATPases, mainly involved in whole body and cellular ion homeostasis, t he gastric H-K-ATPase involved in gastric fluid acidification, and the newl y described nongastric H-K-ATPases for which the identification of physiolo gical roles is still in its infancy. The first member of this last subfamil y was first identified in 1992, rapidly followed by the molecular cloning o f several other members. The relationship between each member remains uncle ar The functional properties of these H-K-ATPases have been studied after t heir ex vivo expression in various functional expression systems, including the Xenopus laevis oocyte, the insect Sig cell line, and the human HEK 293 cells. All these H-K-ATPase oc-subunits appear to encode H-K-ATPases when exogenously expressed in such expression systems. Recent data suggest that these H-K-ATPases could also transport Nat in exchange for K+, revealing a complex cation transport selectivity. Moreover, they display a unique pharm acological profile compared with the canonical Na-K-ATPases or the gastric H-K-ATPase. In addition to their molecular and functional characterizations , a major goal is to correlate the molecular expression of these cloned H-K -ATPases with the native K-ATPases activities described in vivo. This appea rs to be more complex than anticipated. The discrepancies between the funct ional data obtained by exogenous expression of the nongastric H-K-ATPases a nd the physiological data obtained in native organs could have several expl anations as discussed in the present review. Extensive studies will be requ ired in the future to better understand the physiological role of these H-K -ATPases, especially in disease processes including ionic or acid-base diso rders.