Cyclic AMP-dependent protein kinase enhances hippocampal dentate granule cell GABA(A) receptor currents
Cyclic AMP-dependent protein kinase enhances hippocampal dentate granule cell GABA(A) receptor currents
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DOI：
10.1152/jn.1996.76.4.2626
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发表时间：
1996-10-01
影响因子：
2.5
通讯作者：
Macdonald, RL
中科院分区：
文献类型：
--
作者：
Kapur, J;Macdonald, RL
1. 研究了内源性腺苷3′，5′-环单磷酸（cAMP）依赖性蛋白激酶（PKA）的激活、PKA在细胞内的应用以及蛋白激酶抑制肽（PKIP）对内源性PKA的抑制作用对海马齿状颗粒细胞γ -氨基丁酸A（GABA）受体（GABAR）电流的影响。1 mM去甲肾上腺素（52 +/- 26%，平均+/- SE， n = 11）和500 mM 8-溴cAMP （15 +/- 2%, n = 7）可增强GABA（30或100 μ M）诱发的GABAR电流。获得6个齿状颗粒细胞在施用500 μ M 8-溴cAMP前后GABA浓度的响应曲线。最大电流显著增加了89 +/- 36%，但平均EC（50）没有显著变化（68 +/- 42 μ M vs. 25 +/- 10 μ M）。用PKIP和2 mM ATP的移液管记录7个颗粒细胞，并与另一组12个细胞记录2 mM ATP的移液管进行比较，研究GABA浓度的响应关系。当用细胞内PKIP记录电流时，GABA的平均EC（50）没有差异（43 +/- 9 μ M vs. 45 +/- 16 μ M）；然而，获得的最大电流较小（961 +/- 102 pA vs. 658 +/- 104 pA）。使用含有cPKA和ATP再生系统的记录移液管获得4个颗粒细胞的浓度响应数据，并与ATP再生系统记录的7个细胞进行比较。与cPKA相比，GABA的最大电流明显更大（1,224 +/- 132 pA vs. 718 +/- 56 pA），但GABA的EC（50）没有显著改变（21 +/- 2.0 μ M vs. 79 +/- 25 μ M）。
1. The effects of activation of endogenous adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase (PKA), intracellular application of PKA and inhibition of endogenous PKA by protein kinase inhibitory peptide (PKIP) on hippocampal dentate granule cell gamma-aminobuturic acid A (GABA(A)) receptor (GABAR) currents were characterized.2. GABAR currents evoked by repeated application of GABA (30 or 100 mu M) were enhanced by application of 1 mM norepinephrine (52 +/- 26%; mean +/- SE; n = 11) and of 500 mM 8-bromo cAMP (15 +/- 2%, n = 7).3. GABA concentration response curves were obtained from six dentate granule cells before and after application of 500 mu M 8-bromo cAMP. The maximal current was increased significantly by 89 +/- 36%, but the mean EC(50) was not significantly changed (68 +/- 42 mu M vs. 25 +/- 10 mu M).4. The GABA concentration response relationship was studied in a group of 7 granule cells recorded with pipettes containing PKIP and 2 mM ATP and compared with another group of 12 cells recorded with 2 mM ATP in the pipette. When currents were recorded with intracellular PKIP, the mean EC(50) for GABA was no different (43 +/- 9 mu M vs. 45 +/- 16 mu M); however, the maximal current obtained was smaller, (961 +/- 102 pA vs. 658 +/- 104 pA).5. Concentration response data were obtained from four granule cells using recording pipettes containing the cPKA and an ATP regeneration system and compared with seven cells recorded With the ATP regeneration system. With cPKA, the maximal GABAR current was significantly larger (1,224 +/- 132 pA vs. 718 +/- 56 pA), but the EC(50) for GABA was not significantly altered (21 +/- 2.0 mu M vs. 79 +/- 25 mu M).