cAMP-dependent protein kinase modulation of glycine-activated chloride current in neurons freshly isolated from rat ventral tegmental area

Adenosine 3',5'cyclic monophosphate-(cAMP)-dependent protein kinase (PKA) modulation of glycine-activated Cl- currents (I-Gly) in single neurons freshly isolated from the rat ventral tegmental area (VTA) was studied using whole-cell patch-clamp technique. In the majority of cells tested with Mg-ATP in the internal solution, I-Gly induced by 3-10 mu M glycine increased spontaneously (ran up). In the absence of internal ATP, I-Gly remained stable in six of seven cells. External perfusion of 8-Br-cAMP, a PKA activator, potentiated I-Gly only in cells showing run-up. 8-Br-cAMP potentiated I-Gly induced by low concentrations of glycine, but had no effect on the maximal current. When added to the pipette solution, H-89, a PKA inhibitor, blocked ATP and 8-Br-cAMP induced run-up of I-Gly. In contrast, dialysis with chelerythrine, a PKC inhibitor, did not alter the run-up of I-Gly. These results suggest that the PKA pathway modulates the activity of the glycine receptor/channel complex via enhancing the affinity of the receptor for glycine. (C) 1998 Published by Elsevier Science B.V. All rights reserved.