Hypothesis: immature mammals immature mammals, in comparison, exhibit a relative """"""""over-activity"""""""" of H+, K+-ATPase functions, which contributes to the maintenance of a net positive potassium balance. Introduction: The H+, K+-ATPase is an ion transporter which secretes protons and absorbs potassium. The enzyme is compose of an alpha and beta subunit, with four distinct alpha subunits identified. Evidence that immature H+, K+-ATPase is composed of an alpha and beta subunit, with four distinct alpha subunits identified. Evidence that immature H+, K+-ATPase is composed of an alpha and beta subunit, with four distinct alpha subunits identified. Evidence that immature H+, K+-ATPase is regulated differently than adult is found in the only study investigating immature H+, K+-ATPase activity. Immature rabbit cortical collecting duct intercalated cells were investigated and demonstrated H+, K+-ATPase activity similar to that found in mature rabbits. However, two distinct differences were noted. Twice the dose of Sch-28080, an inhibitor of H+, K+-ATPase activity, was required to extinguish immature H+,K+-ATPase activity in comparison to adults. Also, H+,K+-ATPase activity in response to acid loading corrected immature intercalated intracellular pH(pHi) to baseline, while H+,K+-ATPase activity in response to acid loading corrected immature intercalated intracellular pH(pHi) to baseline, while H+, K+-ATPase in mature intercalated cells did not. These differences suggest that H+,K+-ATPase activity in immature mammals is regulated differently than adults.
Specific Aim 1 : To quantify and localize H+,K+-ATPase activity developmentally.
Specific Aim 2 : To determine which HKalpha-isoforms are responsible for H+,K+-ATPase activity in the immature kidney and to follow expression of those isoforms throughout development. Possible candidates include HKalpha1, HKalpha2a, HKalpha2b.
