Ren J, Ye J H, McArdle J J
Departments of Anesthesiology and Pharmacology and Physiology, New Jersey Medical School (UMDNJ), 185 South Orange Avenue, Newark, NJ 07103-2714, USA.
Brain Res. 1998 Nov 16;811(1-2):71-8. doi: 10.1016/s0006-8993(98)00959-7.
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.
采用全细胞膜片钳技术，研究了3',5'-环磷酸腺苷（cAMP）依赖性蛋白激酶（PKA）对从大鼠腹侧被盖区（VTA）新鲜分离的单个神经元中甘氨酸激活的氯离子电流（IGly）的调节作用。在内液中使用Mg-ATP对大多数细胞进行测试时，由3-10 microM甘氨酸诱导的IGly会自发增加（上升）。在没有内源性ATP的情况下，七个细胞中有六个细胞的IGly保持稳定。PKA激活剂8-溴-cAMP的外部灌注仅在显示上升的细胞中增强了IGly。8-溴-cAMP增强了低浓度甘氨酸诱导的IGly，但对最大电流没有影响。当添加到移液管溶液中时，PKA抑制剂H-89阻断了ATP和8-溴-cAMP诱导的IGly上升。相反，用蛋白激酶C（PKC）抑制剂白屈菜红碱进行透析不会改变IGly的上升。这些结果表明，PKA途径通过增强受体对甘氨酸的亲和力来调节甘氨酸受体/通道复合物的活性。
