Effects of Benzamil in Human Cystic Fibrosis Airway Epithelium

Abstract

Cystic fibrosis airway epithelia exhibit a defective transepithelial electrolyte transport. The cyclic adenosine monophosphate stimulated Cl– secretion is abolished because of the loss of the apical membrane cystic fibrosis transmembrane conductance regulator chloride channels. The Na+ absorption is increased drastically because of increased amiloride-sensitive apical Na+ permeability. Here we report that primary cultured human cystic fibrosis nasal epithelium mounted in Ussing chambers showed large transepithelial short-circuit current (Isc). The total Isc was mediated by Na+ conductances and could be blocked entirely by apical application of amiloride with a Ki of 2.73 µM. Benzamil, an analogue of amiloride, also blocked the Isc completely and reversibly, but with a much higher affinity than amiloride. With a Ki of 14 nM and striking lower concentrations than amiloride, benzamil could provide better efficacy in the symptomatic therapy of cystic fibrosis.