The role of phosphorylation in the activity and mercury modulation of GABA-induced currents in rat neurons
The role of phosphorylation in the activity and mercury modulation of GABA-induced currents in rat neurons
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DOI：
10.1016/s0028-3908(97)00172-x
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发表时间：
1997-11-01
影响因子：
4.7
通讯作者：
Narahashi, T
中科院分区：
文献类型：
--
作者：
Huang, CS;Narahashi, T
采用全细胞膜片钳技术，用大鼠背根神经节细胞研究了蛋白激酶 A (PKA) 和蛋白激酶 C (PKC) 在 GABA(A) 受体-氯离子通道复合物的功能和氯化汞调节中的作用。当添加到内部移液管溶液中时，选择性 PKA 抑制剂 KT 5720 和选择性 PKC 抑制剂 calphostin C 均增加了最大电流，并使 GABA 的 EC50 向更高 GABA 浓度的方向移动。通过向内部移液管溶液中添加 5 mM cAMP 以及通过外部灌注 100 nM 佛波醇 13-肉豆蔻酸酯 13-乙酸酯，GABA 激活电流降低。内部应用 5 mM cAMP 可阻断氯化汞对 GABA 激活电流的增强作用。记录移液管中的 PKA 消除了 GABA 激活电流的氯化汞增强作用。相比之下，内部移液管溶液中的0.56μM KT 5720（而不是钙磷蛋白C）增强了氯化汞的效果。总之，PKA 和 PKC 可能通过受体磷酸化负向调节 GABA(A) 受体通道复合物的活性，并且 PKA 系统是氯化汞增强 GABA 激活电流的机制的基础。 (C) 1998 Elsevier Science Ltd. 保留所有权利。
The role of protein kinase A (PKA) and protein kinase C (PKC) in the function and modulation by mercury chloride of the GABA(A) receptor-chloride channel complex was studied with rat dorsal root ganglion cells using the whole-cell patch clamp technique. When added to the internal pipette solutions, both KT 5720, a selective PKA inhibitor, and calphostin C, a selective PKC inhibitor, increased the maximal current and shifted the EC50 for GABA in the direction of higher GABA concentrations. GABA-activated currents were decreased by the addition of 5 mM cAMP to the internal pipette solution, and by external perfusion of 100 nM phorbol 13-myristate 13-acetate. Mercury chloride potentiation of GABA-activated currents was blocked by internal application of 5 mM cAMP. PKA in the recording pipette abolished the mercury chloride potentiation of GABA-activated currents. In contrast, 0.56 mu M KT 5720, but not calphostin C, in the internal pipette solution enhanced the effect of mercury chloride. In conclusion, both PKA and PKC negatively regulate the activity of the GABA(A) receptor-channel complex probably through phosphorylation of the receptor, and the PKA system underlies the mechanism of mercury chloride potentiation of GABA-activated currents. (C) 1998 Elsevier Science Ltd. All rights reserved.