ACTIVATION OF THE BASOLATERAL CL- CONDUCTANCE BY CAMP IN RABBIT RENALPROXIMAL TUBULE S3 SEGMENTS

The regulatory mechanism of basolateral Cl- conductance in rabbit rena l proximal tubule S3 segments was investigated with conventional and C l- sensitive microelectrodes. After the basolateral Cl-/HCO3- exchange r was blocked by 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid ( DIDS) we increased the bath K+ concentration from 5 mmol/l to 20 mmol/ l, which depolarized the cells and thereby increased intracellular Cl- activity ([Cl-](i)). This [Cl-](i) response was enhanced by + 63% in the presence of forskolin (20 mu mol/l), by + 40% in the presence of d ibutyryl adenosine 3',5'-cyclic monophosphate (db-cAMP) (1 mmol/l) and by +44% in the presence of parathyroid hormone (PTH, 10 nmol/l), wher eas it was inhibited by a Cl- channel blocker, indanyl-oxyacetic acid (IAA-94, 0.3 mmol/l). In addition, forskolin, PTH and chlorophenylthio -cAMP enhanced the electrogenic response to removal of bath Cl- after the blockade of K+ conductance, and this activation was also sensitive to IAA-94. On the other hand, 2 mu mol/l ionomycin and 0.5 mu mol/l p horbol myristate failed to activate the [Cl-](i) response to elevation of bath K+ concentration and the electrogenic response to Cl- removal , and ionomycin had no effect even in the absence of DIDS. These resul ts indicate that this basolateral Cl- conductance can be activated by cAMP, while neither the increase in cytosolic Ca2+ nor the activation of protein kinase C has direct effects on this conductance.