Modulation of AMPA/kainate receptors in cultured murine hippocampal neurones by protein kinase C.
Modulation of AMPA/kainate receptors in cultured murine hippocampal neurones by protein kinase C.
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DOI：
10.1113/jphysiol.1994.sp020083
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发表时间：
1994-03
期刊：
影响因子：
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通讯作者：
L. Wang;E. Dudek;M. Browning;J. Macdonald
中科院分区：
文献类型：
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作者：
L. Wang;E. Dudek;M. Browning;J. Macdonald
1.采用膜片钳技术，结合蛋白激酶C催化片段（PKCM）的细胞内灌注，研究该酶在培养的海马神经元中α-氨基-3-羟基-5-甲基-4-异恶唑丙酸酯（AMPA）/红藻氨酸受体的细胞内调节中的作用。 2. 引入 PKCM 增强了接近最大浓度的红藻氨酸 (250 µM) 和 AMPA (100 µM) 引起的反应，而共同应用抑制性肽片段 PKCI(19-36) 则阻止了这种作用。 3. PKCM 对红藻氨酸反应的调节取决于所用激动剂的浓度。红藻氨酸诱发的电流在浓度高于引起最大响应 (EC50) 50% 的浓度时增强，而在较低浓度时减弱。此外，当使用穿孔贴片技术记录红藻氨酸激活的电流时，磷酸酶 1 和 2A 的特异性抑制剂冈田酸对浓度响应关系具有类似的影响。 4.此外，通过细胞内注射PKCM增加了微型兴奋性突触电流(由AMPA/红藻氨酸受体介导)的平均衰减幅度和/或时间常数。 5. 这些观察结果表明，突触后兴奋性氨基酸受体的功能可以通过 PKC 的活性以及内源性磷酸酶来调节。这种调节可能有助于中枢神经系统内某些形式的突触可塑性。
1. The patch clamp technique, together with intracellular perfusion of the catalytic fragment of protein kinase C (PKCM), was employed to investigate the role of this enzyme in the intracellular regulation of alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionate (AMPA)/kainate receptors in cultured hippocampal neurones. 2. The responses evoked by near‐maximal concentrations of kainate (250 microM) and AMPA (100 microM) were potentiated by the introduction of PKCM, whilst co‐application of the inhibitory peptide fragment PKCI(19‐36) prevented this action. 3. Modulation of kainate responses by PKCM was dependent upon the concentration of agonist applied. Currents evoked by kainate were potentiated at concentrations above those which caused 50% of the maximal response (EC50) and depressed at lower concentrations. Furthermore, okadaic acid, a specific inhibitor of phosphatases 1 and 2A, had a similar effect upon concentration‐response relationships when currents activated by kainate were recorded using the perforated patch technique. 4. In addition, the mean amplitude and/or time constant of decay of miniature excitatory synaptic currents (mediated by AMPA/kainate receptors) was increased by the intracellular injection of PKCM. 5. These observations suggest that the function of postsynaptic excitatory amino acid receptors can be modulated by the activity of PKC as well as by endogenous phosphatases. This regulation may contribute to some forms of synaptic plasticity within the central nervous system.