PKA and PKC enhance excitatory synaptic transmission in human dentate gyrus
PKA and PKC enhance excitatory synaptic transmission in human dentate gyrus
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DOI：
10.1152/jn.01031.2002
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发表时间：
2003-05-01
影响因子：
2.5
通讯作者：
Roper, SN
中科院分区：
文献类型：
--
作者：
Chen, HX;Roper, SN
camp依赖性蛋白激酶（PKA）和蛋白激酶C （PKC）是中枢神经系统突触传递的两种主要调节剂，但对它们如何影响中枢神经系统突触传递知之甚少。在这项研究中，我们使用PKC激活剂forskolin和PKC激活剂phorbol酯，使用全细胞记录方法研究了这些激酶对人类海马切片齿状回颗粒细胞突触传递的影响。我们发现福斯可林和佛波酯都增加了自发和微型兴奋性突触后电流（sEPSCs和mEPSCs）的频率，但幅度不受影响。失活的福斯克林和佛博尔酯对人齿状颗粒细胞sEPSCs无影响。先前使用福斯克林阻断了佛波酯对mEPSC频率的影响。穿孔通路的强电刺激引起齿状回颗粒细胞的短期抑制。福斯克林和佛波酯均能显著增强这种短期抑郁。综上所述，这些结果表明PKA和PKC主要通过突触前机制参与了人齿状颗粒细胞兴奋性突触传递的上调。此外，阻断实验表明，这两种激酶可能共享一个共同的信号通路。
cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) are two major modulators of synaptic transmission in the CNS but little is known about how they affect synaptic transmission in the human CNS. In this study, we used forskolin, a PKA activator, and phorbol ester, a PKC activator, to examine the effects of these kinases on synaptic transmission in granule cells of the dentate gyrus in human hippocampal slices using whole-cell recording methods. We found that both forskolin and phorbol ester increased the frequency of spontaneous and miniature excitatory postsynaptic currents (sEPSCs and mEPSCs) but left the amplitude unaffected. Inactive forskolin and phorbol ester had no effect on sEPSCs in human dentate granule cells. Prior application of forskolin occluded the effects of phorbol ester on mEPSC frequency. Tetanic stimulation applied to the perforant path induced short-term depression in dentate gyrus granule cells. Both forskolin and phorbol ester significantly enhanced this short-term depression. Taken together, these results demonstrate that PKA and PKC are involved in up-regulation of excitatory synaptic transmission in human dentate granule cells, primarily by presynaptic mechanisms. In addition, the occlusion experiments suggest that the two kinases may share a common signal pathway.