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

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 x 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. Ca2+-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 Ca2+-dependent Cl--channels with an inhibition of Na+-channel activity or absorption in rabbit tracheal epithelium. (C) 1997 Elsevier Science B.V.