The renal H,K-ATPases

Purpose of review We integrate recent evidence that demonstrates the importance of the gastric (HK alpha 1) and nongastric (HK alpha 2)-containing hydrogen potassium adenosine triphosphatases (H, K-ATPases) on physiological function and their role in potassium (K), sodium (Na), and acid-base balance. Recent findings Previous studies focused on the primary role of H, K-ATPases as a mechanism of K conservation during states of K deprivation. Both isoforms function in H secretion and K absorption in vivo during K deprivation, but recent findings show that these pumps also function in acid secretion in animals fed normal K-replete diets. The complicated pharmacological inhibition of both pumps is reviewed. Interestingly, HK alpha 2-null mice have a reduced expression and activity of the renal epithelial Na channel a subunit in the colon. When the human nongastric isoform was studied in a heterologous expression system with its cognate beta subunit (NaK beta 1), the pump exhibited substantial Na affinity at the 'K'-binding site. Evidence cited herein raises the possibility that either directly or indirectly the renal HK alpha 2-containing H,K-ATPase may affect Na balance. Summary Both H, K-ATPase isoforms are active in normal animals and not just under conditions of K depletion. The possibility that either one or both isoforms contribute to Na absorption, particularly in humans, raises important clinical implications for these pumps in the kidney.