ATP-induced Cl − secretion with suppressed Na + absorption in rabbit tracheal epithelium

Abstract

The effect of extracellular ATP on ion transport of rabbit tracheal epithelium was examined using an Ussing chamber. Isoproterenol (10 −8–10 −5 M) did not alter the electrophysiological properties across the tracheal epithelium. Apically applied ATP induced an initial transient increase in short circuit current (SCC) followed by a decline to below the prior baseline. The initial increase by ATP (10 −4 M) was significantly inhibited by a Cl −-channel inhibitor diphenylamine-2-carboxylate (DPC, 5×10 −4 M) and Cl −-substitution with gluconate in the bath solution, while a cystic fibrosis transmembrane regulator (CFTR) Cl −-channel inhibitor glibenclamide (10 −4 M), a Na +-channel inhibitor amiloride (10 −4 M) and a K +-channel inhibitor quinidine (10 −4 M) all failed to alter it. The decline in SCC by ATP was abolished by amiloride, while DPC or Cl −-substitution with gluconate in the bath solution did not alter it. Ca 2+-removal from the bath solutions did not significantly alter the initial increase nor the decline by ATP. Ionomycin (10 −5 M) induced an initial transient increase in SCC, to a degree similar to that by ATP alone. A calmodulin antagonist W-7 reduced the SCC baseline and abolished SCC increase by ATP. These findings indicate that ATP activates Ca 2+-dependent Cl −-channels with an inhibition of Na +-channel activity or absorption in rabbit tracheal epithelium.