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Zinc modulation of glycine receptors in acutely isolated rat CA3 neurons.

机译:急性分离的大鼠CA3神经元中甘氨酸受体的锌调节。

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Glycine and GABA are the primary inhibitory neurotransmitters in the spinal cord and brain stem, with glycine exerting its physiological roles by activating strychnine-sensitive ionotropic receptors. Glycine receptors are also expressed in the brain, including the cortex and hippocampus, but their physiological roles and pharmacological properties are largely unknown. Here, we report the pharmacological properties of functional glycine receptors in acutely isolated rat CA3 neurons using conventional whole-cell patch clamp techniques. Both glycine and taurine, which are endogenous agonists of glycine receptors, elicited Cl(-) currents in a concentration-dependent manner. The glycine-induced current (I(Gly)) was inhibited by strychnine, picrotoxin or cyclothiazide in a concentration-dependent manner. At lower concentrations (0.01-1 microM), ICS-205,930 potentiated I(Gly), but at higher concentrations (>10 microM) it inhibited I(Gly). These pharmacological properties strongly suggest that CA3 neurons express functional strychnine-sensitive glycine receptors containing alpha2 subunits. Furthermore, at lower concentrations (1-30 microM), Zn(2+) potentiated I(Gly), but at higher concentrations (>100 microM) it inhibited I(Gly). Considering that Zn(2+) is synaptically co-released with glutamate from mossy fiber terminals that make excitatory synapses onto CA3 neurons, these results suggest that endogenous Zn(2+) modulation of these glycine receptors may have an important role in the excitability of CA3 neurons.
机译:甘氨酸和GABA是脊髓和脑干中的主要抑制性神经递质,甘氨酸通过激活对苯丙氨酸敏感的离子型受体发挥其生理作用。甘氨酸受体也在包括皮层和海马体在内的大脑中表达,但是它们的生理作用和药理特性尚不清楚。在这里,我们报告使用常规的全细胞膜片钳技术在急性分离的大鼠CA3神经元中功能性甘氨酸受体的药理特性。甘氨酸和牛磺酸都是甘氨酸受体的内源性激动剂,它们均以浓度依赖的方式引起Cl(-)电流。甘氨酸诱导的电流(I(Gly))被苯丙氨酸,微毒素或环噻嗪以浓度依赖的方式抑制。在较低浓度(0.01-1 microM)下,ICS-205,930增强了I(Gly),但在较高浓度(> 10 microM)下,它抑制了I(Gly)。这些药理特性强烈表明,CA3神经元表达了含有α2亚基的功能性对苯丙氨酸敏感的甘氨酸受体。此外,在较低浓度(1-30 microM)下,Zn(2+)增强了I(Gly),但在较高浓度(> 100 microM)下,它抑制了I(Gly)。考虑到Zn(2+)与苔藓纤维末端的谷氨酸突触共释放,从而使兴奋性突触作用于CA3神经元,这些结果表明,这些甘氨酸受体的内源性Zn(2+)调节可能在以下物质的兴奋性中起重要作用: CA3神经元。

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