Activation of chloride currents in choroid plexus by GTP-gamma-S and cyclic-AMP

The regulation of a Cl- conductance in the choroid plexus by G proteins was investigated using whole-cell patch clamp methods. A transient Cl- current was evoked when GTP-gamma-S (0.1 mM) was included in the electrode solution. The GTP-gamma-S-evoked current was only observed when 2 mM ATP was present in the electrode solution, and was inhibited in the presence of 2 mM GDP-beta-S. The activated current was shown to be Cl(-)-selective in ion replacement studies, and exhibited inward-rectification. The current was not inhibited when intracellular Ca2+ was strongly buffered with either EGTA or BAPTA, suggesting that the current was not activated by a change in intracellular Ca2+. The effects of GTP-gamma-S were mimicked, however, when cyclic AMP or the catalytic-subunit of protein kinase A were included in the electrode solution. These data suggest that G proteins activate Cl- channels via a cAMP-dependent pathway in rat choroid plexus.