H-K-ATPase type 2: relevance for renal physiology and beyond

Abstract

H-K-ATPase type 2 (HKA2), also known as the “nongastric” or “colonic” H-K-ATPase, is broadly expressed, and its presence in the kidney has puzzled experts in the field of renal ion transport systems for many years. One of the most important and robust characteristics of this transporter is that it is strongly stimulated after dietary K+ restriction. This result prompted many investigators to propose that it should play a role in allowing the kidney to efficiently retain K+ under K+ depletion. However, the apparent absence of a clear renal phenotype in HKA2-null mice has led to the idea that this transporter is an epiphenomenon. This review summarizes past and recent findings regarding the functional, structural and physiological characteristics of H-K-ATPase type 2. The findings discussed in this review suggest that, as in the famous story, the ugly duckling of the X-K-ATPase family is actually a swan.

An Integrated View of Potassium Homeostasis

“…2 Much evidence supports the role of the circadian clock in external homeostasis, and some evidence indicates a role in internal homeostasis. 7,12-14 …”

Physiological and molecular responses of the spiny dogfish shark (Squalus acanthias) to high environmental ammonia: scavenging for nitrogen

“…An alternative or additional possibility would be active apical NH 4 + uptake via substitution on the K + site of H + /K + -ATPase, which has been identified in elasmobranch gills (Choe et al, 2004). NH 4 + is well known to be able to substitute for K + in a variety of transport systems, including members of this family of transport ATPases (Codina et al, 1999; Cougnon et al, 1999;Crambert, 2014).…”

“…An alternative or additional possibility would be active apical NH 4 + uptake via substitution on the K + site of H + /K + -ATPase, which has been identified in elasmobranch gills (Choe et al, 2004). NH 4 + is well known to be able to substitute for K + in a variety of transport systems, including members of this family of transport ATPases (Codina et al, 1999; Cougnon et al, 1999;Crambert, 2014).How relevant is the present ammonia exposure scenario to real world conditions? The water T Amm level used in our tests (1000 μmol l −1 ) was chosen for comparison to the many previous HEA studies on teleosts using a similar level, as cited above.…”

Parameter estimation for mathematical models of a nongastric H+(Na+)-K+(NH4+)-ATPase

“…, it is even closer to the ␣-subunit of gastric HKA (11). Furthermore, pharmacological profiles have suggested that rat nongastric HKA shares more similarities with rat Na (9), and the rabbit gastric ␤-subunit (rg␤HKA).…”