The colonic (HKalpha2) H+,K+ ATPase and the effects of aldosterone in the kidney.

摘要

The kidney is the organ largely responsible for maintenance of ion and acid-base balance. The H+, K+ ATPase is one of the many enzymes the kidney employs to carry out these functions. The H +, K+ ATPase utilizes the energy of ATP hydrolysis to pump K+ into the cells of the renal collecting duct in exchange for H+, transporting both ions against their concentration gradients. Evidence suggests that the colonic H+, K+ ATPase, or HKalpha2 isoform, plays an important role in K+ conservation by the kidney. Two HKalpha2 isoforms, designated HKalpha2a and HKalpha2c, have been identified in the rabbit kidney. The mineralocorticoid aldosterone also acts in the collecting duct of the kidney; it is responsible for maintaining Na+ balance, acid-base balance, and blood pressure. It was the goal of this dissertation to gain a better understanding of renal ion transport and its hormonal regulation. To that end, we have created a molecular model of the HKalpha2a subunit (Specific Aim 1), cloned the four known mammalian X+, K+ ATPase beta subunits that may pair with HKalpha2a and HKalpha2c (Specific Aim 2), established a mammalian expression system for the rabbit colonic H +, K+ ATPase (Specific Aim 3), identified the beta subunit of the gastric H+, K+ ATPase as the putative partner of HKalpha2a and HKalpha2c by co-immunoprecipitation (Specific Aim 4), and characterized the early effects of aldosterone on gene expression in the mouse inner medullary collecting duct (Specific Aim 5).