Acute regulation of Na+/H+ exchange, Na+:HCO3- cotransport, and C1-/base exchange in acid base disorders

The aim of these experiments was to study acute regulation of proximal tubule H+/HCO3- transport systems in acid-base disorders. Proximal tubular suspensions were prepared from rabbit kidney cortex and incubated in acidic (pH 6.9), control (pH 7.4), or alkalotic (pH 8.0) media for 45 minutes and gassed with 5% CO2. Brush border membrane (BBM) and basolateral membrane (BLM) vesicles were isolated from the tubular suspensions and studied for the activity of the pH-regulating transport systems. Influx of amiloride-sensitive 22Na at 10 seconds (pHo 7.5, pHi 6.0) into BBM vesicles was 36% higher in the acidotic and 51% lower in alkalotic groups compared to control. HCO3-dependent 22Na uptake was increased by 55% in BLM vesicles from acidotic and remained unchanged in ones from alkalotic tubules. The presence of 250 nmol/L staurosporine during incubation in acidic medium reduced the activities of Na+/H+ exchange and Na+/HCO3- cotransport by 19% and 17%, respectively. 36Chloride influx into BBM vesicles (mediated via Cl-/Cl- exchange) remained unchanged in vesicles harvested from tubules in acidic and alkalotic media. However, 36chloride influx into BLM vesicles (mediated via Cl-/Cl- exchange) decreased by 23% in the acidic and increased by 37% in the alkalotic group. Staurosporine had no effect on Cl/base exchange in BLM vesicles isolated from control, acidotic, or alkalotic tubules. We conclude that in vitro acid-base disorders are associated with complex and preferential adaptive changes in certain pH-regulating processes in kidney proximal tubules. Some of these effects are partially mediated via protein kinase C.