the epithelial sodium channel (enac) establishes a trafficking vesicle pool responsible for its regulation上皮细胞钠离子通道(钠)建立了一个贩卖泡池负责监管.pdf

The Epithelial Sodium Channel (ENaC) Establishes a Trafficking Vesicle Pool Responsible for Its Regulation 1 2 1 1,2 1,2 Robert S. Edinger , Carol A. Bertrand , Christine Rondandino , Gerard A. Apodaca , John P. Johnson , Michael B. Butterworth2* 1 Department of Medicine, Renal-Electrolyte Division, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America, 2 Department of Cell Biology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America Abstract The epithelial sodium channel (ENaC) is the rate-limiting step for sodium reabsorption across tight epithelia. Cyclic-AMP (cAMP) stimulation promotes ENaC trafficking to the apical surface to increase channel number and transcellular Na+ transport. Removal of corticosteroid supplementation in a cultured cortical collecting duct cell line reduced ENaC expression. Concurrently, the number of vesicles trafficked in response to cAMP stimulation, as measured by a change in membrane capacitance, also decreased. Stimulation with aldosterone restored both the basal and cAMP-stimulated ENaC activity and increased the number of exocytosed vesicles. Knocking down ENaC directly decreased both the cAMP- stimulated short-circuit current and capacitance response in the presence of aldosterone. However, constitutive apical recycling of the Immunoglobulin A receptor was unaffected by alterations in ENaC expression or trafficking. Fischer Rat Thyroid cells, transfected with a,b,c-mENaC had a significantly greater membrane capacitance response