Bicarbonate transport across the frog choroid plexus and its control by cyclic nucleotides

We have studied the effects of ions, hormones, diuretics and cyclic nucleotides on the short-circuit current (Isc) across the frog choroid plexus. In normal HCO3 Ringer solution, the trans-epithelial potential difference (p.d.), Isc and resistance (Rt) were -0.8 mV (ventricular side negative with respect to to the blood (serosal) side), 6 microA/cm2 and 170 omega cm2, respectively. Removal of Na, Cl or HCO3 from the solution decreased the Isc to 1.9, 2.3 or -4.6 microA/cm2, respectively. Theophylline, dibutyryl cyclic AMP, isoproterenol, prostaglandin E1, ACTH, cholera toxin and forskolin all significantly increased the Isc. The theophylline-induced change in Isc (delta Itheosc) was reduced by 50% upon Cl substitution with gluconate, and was abolished to less than 12% by Na-free and HCO3-free solutions. pH monitoring of the bathing solutions showed that acidification of the serosal bathing fluid was enhanced by theophylline while that of the ventricular solution was retarded. Ouabain, acetazolamide, SITS, DIDS and furosemide inhibited both Isc and delta Itheosc. We conclude that HCO3 secretion by the choroid plexus into the c.s.f. is controlled by hormones which stimulate the adenylate cyclase system, and propose a model of ion transport across the choroidal epithelium.