APICAL REGULATION OF NONSELECTIVE CATION CHANNELS BY ATP IN LARVAL BULLFROG SKIN

The apical membrane of larval bullfrog skin contains a nonselective ca tion channel that can be activated by apically applied amiloride and a cetylcholine. In our search for other ligands that might activate this channel, ATP and other purinergics were tested. When ATP (10-1,000 mu M) was added to the apical side of tadpole skin mounted in a modified Ussing chamber, there was a transient increase in short circuit curre nt (Isc). The increase in Isc occurred with either Na or K as the domi nant cation in the apical solution. The response was larger in a calci um-free Ringer. ADP and AMP had similar but smaller effects than ATP. Adenosine and UTP were without effect. The ATP response was blocked by W-7, atropine, curare, diltiazem, and suramin. These blockers also in hibit amiloride stimulation of Isc, suggesting that ATP activates a re lated transport pathway. Studies with analogs of ATP suggest that the ATP binding site in tadpole skin has characteristics in common with th e P2x receptor found in other tissues. These results demonstrate that in addition to amiloride and acetylcholine, ATP stimulates cation tran sport at the apical membrane of larval amphibian skin epithelia. (C) 1 997 Wiley-Liss, Inc.