EFFECTS OF EXTRACELLULAR ATP ON ION-TRANSPORT AND [CA2-EAR EPITHELIUM(](I) IN MONGOLIAN GERBIL MIDDLE)

The present study investigates the effects of ATP on ion transport and Ca2+ mobilization in primary cultures of gerbil middle ear epithelium . Extracellular ATP and other nucleotides elicited a transient increas e in short-circuit current (I-sc) in a dose-dependent manner. The rank order of potency in I-sc responses corresponded with the sequence of the P-2u purinergic gic receptor when applied to the mucosal or the ba solateral side. Extracellular ATP induced a rise in the intracellular Ca2+ concentration ([Ca2+](i)) in a dose-dependent manner. A similar r ank order of potency in the ATP-induced increases in [Ca2+](i) was obs erved. The time courses of the [Ca2+](i) responses induced by ATP clos ely paralleled those of the I-sc responses. 2-Bis(2-aminophenoxy)ethan e-N,N,N',N'-tetra-acetic acid acetoxymethyl ester greatly reduced the increase in the I-sc and [Ca2+](i) responses to ATP. Diphenylamine-2-c arboxylate, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, quinidin e, and Ba2+ significantly blocked the ATP-stimulated I-sc. Glibenclami de had no effect on the ATP-stimulated I-sc. These results are consist ent with the hypothesis that extracellular ATP and other nucleotides i nduce Cl- secretion across the apical membrane in cultured gerbil midd le ear epithelium by activation of the apical Cl- channels via multipl e modes of regulation.