Zinc enhances the inhibitory effects of strychnine-sensitive glycine receptors in mouse hippocampal neurons.
Zinc enhances the inhibitory effects of strychnine-sensitive glycine receptors in mouse hippocampal neurons.
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DOI：
10.1152/jn.00500.2007
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发表时间：
2007-12
影响因子：
2.5
通讯作者：
Hai Xia Zhang;L. Thio
中科院分区：
文献类型：
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作者：
Hai Xia Zhang;L. Thio
虽然细胞外Zn（2+）是士的宁敏感的甘氨酸受体（GlyRs）的内源性双相调节剂，但这种调节的生理意义仍然知之甚少。在突触前Zn（2+）丰富的海马中，Zn（2+）对GlyR的调节可能特别重要。使用培养的胚胎小鼠海马神经元，我们检查是否1 μ M的Zn（2+），增强浓度，增强持续甘氨酸应用激活的GlyRs的抑制作用。单独持续应用20 μ M甘氨酸（EC（25））并没有减少去极化步骤诱发的动作电位数量，但在1 μ M Zn（2+）中却减少了。这种效应至少有一部分是由于Zn（2+）增强了GlyR诱导的输入电阻降低而产生的。单独持续应用20 μ M甘氨酸不会改变神经元爆发，这是一种通过忽略细胞外Mg（2+）诱导的过度兴奋形式。然而，持续应用20 μ M甘氨酸会抑制1 μ M Zn（2+）中的神经元爆发。在这些范例中，Zn（2+）没有增强持续60 μ M甘氨酸（EC（70））应用的抑制作用。这些结果表明，紧张性GlyR激活可以降低神经元的兴奋性。为了验证这种可能性，我们研究了GlyR拮抗剂士的宁和Zn（2+）螯合剂tricine对小鼠海马脑片CA 1锥体神经元动作电位放电的影响。共同应用士的宁和tricine轻微，但显着增加了动作电位发射的数量在去极化电流步骤，并降低了基强度的动作电位发射。因此，Zn（2+）可以调节神经元的兴奋性正常和在病理条件下，如癫痫发作，通过增强GlyR紧张激活低浓度的激动剂。
Although extracellular Zn(2+) is an endogenous biphasic modulator of strychnine-sensitive glycine receptors (GlyRs), the physiological significance of this modulation remains poorly understood. Zn(2+) modulation of GlyR may be especially important in the hippocampus where presynaptic Zn(2+) is abundant. Using cultured embryonic mouse hippocampal neurons, we examined whether 1 microM Zn(2+), a potentiating concentration, enhances the inhibitory effects of GlyRs activated by sustained glycine applications. Sustained 20 microM glycine (EC(25)) applications alone did not decrease the number of action potentials evoked by depolarizing steps, but they did in 1 microM Zn(2+). At least part of this effect resulted from Zn(2+) enhancing the GlyR-induced decrease in input resistance. Sustained 20 microM glycine applications alone did not alter neuronal bursting, a form of hyperexcitability induced by omitting extracellular Mg(2+). However, sustained 20 microM glycine applications depressed neuronal bursting in 1 microM Zn(2+). Zn(2+) did not enhance the inhibitory effects of sustained 60 microM glycine (EC(70)) applications in these paradigms. These results suggest that tonic GlyR activation could decrease neuronal excitability. To test this possibility, we examined the effect of the GlyR antagonist strychnine and the Zn(2+) chelator tricine on action potential firing by CA1 pyramidal neurons in mouse hippocampal slices. Co-applying strychnine and tricine slightly but significantly increased the number of action potentials fired during a depolarizing current step and decreased the rheobase for action potential firing. Thus Zn(2+) may modulate neuronal excitability normally and in pathological conditions such as seizures by potentiating GlyRs tonically activated by low agonist concentrations.