Forskolin activates gated Cl- channels in frog skin.

We investigated the effect of forskolin on Cl- movements across the isolated epithelium of frog skin. With Cl- on both sides, forskolin (50 mumol/l) increased the transepithelial conductance considerably and elicited significant Cl- secretion. Establishing transepithelial Cl- gradients markedly increased the Cl- currents (ICl). During forskolin treatment, the power density spectra (PDS) of the fluctuation in transepithelial current contained a Lorentzian component that depended on the presence of Cl- in the bathing solutions. Mucosal as well as serosal diphenylamine-2-carboxylic acid (DPC; 1 mmol/l) partially depressed ICl as well as the Lorentzian noise component. Microelectrode recordings from cells involved in transepithelial Na+ absorption showed that forskolin activates gated Cl- channels in a cellular pathway in parallel with the Na+-transporting granulosum cells of the frog skin. The activation of the Cl- -dependent currents and Lorentzian noise was rather variable, and adaptation of the animals to solutions that contained 40 or 60 mmol/l NaCl increased the sensitivity to forskolin. In skins of salt-adapted animals, oxytocin (0.1 U/ml) also slightly activated the Cl- pathway. On the other hand, oxytocin and 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate (CPT-cAMP; 1 mmol/l) were without effect in control skins.