EFFECTS OF BENZAMIL IN HUMAN CYSTIC-FIBROSIS AIRWAY EPITHELIUM

Cystic fibrosis airway epithelia exhibit a defective transepithelial e lectrolyte transport. The cyclic adenosine monophosphate stimulated Cl - secretion is abolished because of the loss of the apical membrane cy stic fibrosis transmembrane conductance regulator chloride channels. T he Na+ absorption is increased drastically because of increased amilor ide-sensitive apical Na+ permeability. Here we report that primary cul tured human cystic fibrosis nasal epithelium mounted in Ussing chamber s showed large transepithelial short-circuit current (I-sc). The total I-sc was mediated by Na+ conductances and could be blocked entirely b y apical application of amiloride with a K-i of 2.73 mu M. Benzamil, a n analogue of amiloride, also blocked the I-sc completely and reversib ly, but with a much higher affinity than amiloride. With a K-i of 14 n M and striking lower concentrations than amiloride, benzamil could pro vide better efficacy in the symptomatic therapy of cystic fibrosis.