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Effects of Ca 2+ channel blockers on amiloride-sensitive Na + permeable channels and Na + transport in fetal rat alveolar type II epithelium

Biochemical Pharmacology, ISSN: 0006-2952, Vol: 63, Issue: 8, Page: 1547-1552
2002
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A β-adrenergic agonist (β-agonist), terbutaline, stimulated amiloride-sensitive Na + absorption in fetal rat alveolar type II epithelium, contributing to the clearance of lung fluid. Cytosolic Ca 2+ plays an important role in terbutaline-stimulated Na + absorption, since Ca 2+ -activated, amiloride-sensitive Na + -permeable channels are involved in transcellular Na + absorption and terbutaline stably elevates the cytosolic Ca 2+ concentration by stimulating Ca 2+ influx. Therefore, we studied whether Ca 2+ channel blockers (Ni 2+, verapamil, and nifedipine) affect terbutaline-stimulated transcellular Na + absorption. Ni 2+ partially blocked the channel responsible for the terbutaline-stimulated Na + absorption at the Na + entry pathway across the apical membrane of the epithelium, but did not diminish the terbutaline-stimulated transcellular Na + absorption. By measuring the capacity of the Na +,K + -pump activity, we determined that the rate-limiting step of the terbutaline-stimulated transcellular Na + absorption was the extrusion step across the basolateral membrane by the Na +,K + -pump. The other Ca 2+ channel blockers, verapamil and nifedipine, had effects identical to those of Ni 2+. Based upon these observations, we conclude that, in the β-agonist-stimulated fetal rat alveolar type II epithelium, Ca 2+ channel blockers diminish amiloride-sensitive channels, but do not affect transcellular Na + absorption, since under the β-agonist-stimulated condition the Na +,K + -pump is the rate-limitng step in Na + transport.

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