ANION SECRETION BY THE INNER MEDULLARY COLLECTING DUCT - EVIDENCE FORINVOLVEMENT OF THE CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR

It is well established that the terminal renal collecting duct is capa ble of electrogenic Na+ absorption. The present experiments examined o ther active ion transport processes in primary cultures of the rat inn er medullary collecting duct. When the amiloride analogue benzamil inh ibited electrogenic Na+ absorption, cAMP agonists stimulated a trans-m onolayer short circuit current that was not dependent on the presence of Na+ in the apical solution, but was dependent on the presence of Cl - and HCO3-. This current was not inhibited by the loop diuretic bumet anide, but was inhibited by ouabain, an inhibitor of the Na+/K+ pump. The current was reduced by anion transport inhibitors, with a profile similar to that seen for inhibitors of the cystic fibrosis transmembra ne conductance regulator (CFTR) Cl- channel. Using several PCR strateg ies, we demonstrated fragments of the predicted lengths and sequence i dentity with the rat CFTR. Using whole-cell patch-clamp analysis, we d emonstrated a cAMP-stimulated Cl- current with characteristics of the CFTR. We conclude that the rat inner medullary collecting duct has the capacity to secrete anions. It is highly likely that the CFTR Cl- cha nnel is involved in this process.