Neuroprotectant minocycline depresses glutamatergic neurotransmission and Ca2+ signalling in hippocampal neurons
Neuroprotectant minocycline depresses glutamatergic neurotransmission and Ca2+ signalling in hippocampal neurons
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DOI：
10.1111/j.1460-9568.2007.05873.x
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发表时间：
2007-11-01
影响因子：
3.4
通讯作者：
Hernandez-Guijo, Jesus M.
中科院分区：
文献类型：
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作者：
Gonzalez, Jose Carlos;Egea, Javier;Hernandez-Guijo, Jesus M.
四环素类抗生素米诺环素对各种神经元损伤的神经保护作用的机制是有争议的。在试图澄清这一机制，我们在这里研究了其对各种电生理参数，Ca 2+信号，谷氨酸释放，在原代培养的大鼠海马神经元，在突触体的影响。自发兴奋性突触后电流和动作电位放电显着降低米诺环素在已知的浓度提供神经保护。该药物还阻断全细胞内向Na+电流（I-Na）20%，全细胞Ca 2+电流（I-Ca）约30%。米诺环素抑制谷氨酸诱发的胞浆Ca 2+浓度升高近40%，抑制K+诱发的突触体谷氨酸释放63%。米诺环素也抑制自发兴奋性突触后电流的频率和幅度，但不影响γ-氨基丁酸或谷氨酸引起的全细胞内向电流。这种药理学特征表明米诺环素的神经保护作用可能与神经元兴奋性、谷氨酸释放和Ca 2+超载的缓解有关。
The mechanism of the neuroprotective action of the tetracycline antibiotic minocycline against various neuron insults is controversial. In an attempt to clarify this mechanism, we have studied here its effects on various electrophysiological parameters, Ca2+ signalling, and glutamate release, in primary cultures of rat hippocampal neurons, and in synaptosomes. Spontaneous excitatory postsynaptic currents and action potential firing were drastically decreased by minocycline at concentrations known to afford neuroprotection. The drug also blocked whole-cell inward Na+ currents (I-Na) by 20%, and the whole-cell Ca2+ current (I-Ca) by about 30%. Minocycline inhibited glutamate-evoked elevation of the cytosolic Ca2+ concentration ([Ca2+](c)) by nearly 40%, and K+-evoked glutamate release from synaptosomes by 63%. Minocycline also depressed the frequency and amplitude of spontaneous excitatory postsynaptic currents, but did not affect the whole-cell inward current elicited by gamma-aminobutyric acid or glutamate. This pharmacological profile suggests that the neuroprotective effects of minocycline might be associated with the mitigation of neuronal excitability, glutamate release, and Ca2+ overloading.