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 (IGly) 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, IGly induced by 3-10 microM glycine increased spontaneously (ran up). In the absence of internal ATP, IGly remained stable in six of seven cells. External perfusion of 8-Br-cAMP, a PKA activator, potentiated IGly only in cells showing run-up. 8-Br-cAMP potentiated IGly 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 IGly. In contrast, dialysis with chelerythrine, a PKC inhibitor, did not alter the run-up of IGly. 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.
Ren
J
J
Departments of Anesthesiology and Pharmacology and Physiology, New Jersey Medical School (UMDNJ), 185 South Orange Avenue, Newark, NJ 07103-2714, USA.
Ye
J H
JH
McArdle
J J
JJ
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D018118:Chloride Channels / Q000502:physiology*; D002712:Chlorides / Q000493:pharmacokinetics; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D004058:Diffusion; D066298:In Vitro Techniques; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D018009:Receptors, Glycine / Q000502:physiology*; D017557:Ventral Tegmental Area / Q000166:cytology / Q000502:physiology*
D018118:Chloride Channels; D002712:Chlorides; D018009:Receptors, Glycine; D000255:Adenosine Triphosphate; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C