Benzamil-induced conductive state of insulin-stimulated, amiloride-blockable cation channel in fetal lung epithelium.

Insulin activated a 28 pS amiloride-blockable nonselective cation (NSC) channel in rat fetal distal lung epithelium. Benzamil, an analogue of amiloride, decreased the open probability (Po) of the insulin-unstimulated channel from 0.06 +/- 0.02 to 0.0013 +/- 0.0006 (mean +/- SEM, n = 5-7; 100 microM benzamil application to extracellular surface), but increased the Po of the insulin-stimulated channel from 0.10 +/- 0.02 to 0.69 +/- 0.02 (mean +/- SEM, n = 5-7; 100 microM benzamil application to extracellular surface). The effects of benzamil could be observed in either case that it was applied to the extracellular or cytosolic surface. Unlike benzamil, amiloride decreased the Po of both insulin-unstimulated and -stimulated channels. These observations suggest that benzamil acts as a blocker on the insulin-unstimulated NSC channel but as an opener on the insulin-stimulated NSC channel.