Evidence for amiloride-sensitive sodium channels in alveolar epithelial cells.
To maintain alveolar air spaces relatively fluid free, the alveolar epithelium appears capable of vectorial transport of water and solutes. Active transepithelial transport of sodium by alveolar epithelial cell monolayers has previously been demonstrated, indicating that alveolar pneumocytes must possess ion transport mechanisms by which sodium can enter the cells apically for subsequent extrusion via Na(+)-K(+)-adenosinetriphosphatase activity at the basolateral surface. In this study, sodium entry mechanisms were investigated by directly measuring 22Na uptake into rat alveolar epithelial cells grown in primary culture. Cells exhibited increasing 22Na uptake with time over a 30-min interval. Total sodium uptake was compared in the presence and absence of several sodium transport inhibitors. Uptake was inhibited by the sodium channel blockers amiloride and benzamil but was not affected by two amiloride analogues (bromohexamethylene amiloride and dimethylamiloride) with diminished specificity for blocking sodium channels and enhanced specificity for inhibiting the Na(+)-H+ antiporter. Uptake was also unaffected by the chloride transport inhibitor bumetanide or by the absence of glucose. These data suggest that sodium uptake occurs primarily via sodium channel and that Na(+)-H+ antiport, Na(+)-K(+)-2Cl- cotransport, and Na(+)-glucose cotransport do not contribute significantly to sodium uptake under these experimental conditions. The presence of sodium channels in the alveolar epithelial cell membrane may provide the major entry mechanism by which sodium enters these cells for subsequent active extrusion, thereby effecting net salt and water reabsorption from the alveolar spaces.
Russo
R M
RM
Will Rogers Institute Pulmonary Research Center, Division of Pulmonary and Critical Care Medicine, University of Southern California, Los Angeles 90033.
Lubman
R L
RL
Crandall
E D
ED
D000143:Acids / Q000378:metabolism; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*; D012964:Sodium / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics; D015222:Sodium Channels / Q000187:drug effects*
D000143:Acids; D015222:Sodium Channels; C013407:benzamil; C039465:5-dimethylamiloride; D010042:Ouabain; D000584:Amiloride; D012964:Sodium; D005947:Glucose