Spontaneous, synchronous zinc spikes oscillate with neural excitability and calcium spikes in primary hippocampal neuron culture.
Spontaneous, synchronous zinc spikes oscillate with neural excitability and calcium spikes in primary hippocampal neuron culture.
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自发的，同步的锌尖峰振荡与神经兴奋性和原发性海马神经元培养物中的钙尖峰。
DOI：
10.1111/jnc.15334
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发表时间：
2021-06
影响因子：
4.7
通讯作者：
Qin Y
中科院分区：
文献类型：
--
作者：
Zhang C;Maslar D;Minckley TF;LeJeune KD;Qin Y
由于锌对包括酶、转录因子、离子通道、神经营养因子和突触后支架蛋白在内的众多蛋白质靶点具有调节作用，它被认为可作为一种细胞内信号分子。然而，在自然生理条件下，细胞内锌浓度被严格维持在稳定水平。细胞内锌浓度的动态变化仅在某些暴露于病理刺激或受体配体结合时的细胞类型中被检测到。与钙这种在各种细胞中能周期性且自发振荡的普遍存在的信号金属离子不同，锌的自发振荡从未被报道过。在这项工作中，我们有了新的发现：在原代海马培养物中，使用荧光锌传感器FluoZin - 3观察到发育中的神经元会产生自发且同步的锌峰。阻断谷氨酸受体依赖性钙内流会使锌峰消失，这表明这些锌峰是由谷氨酸介导的自发神经兴奋性以及在早期发育神经元中已被表征的钙峰所驱动的。通过对钙或pH与锌同时成像，我们发现每次锌峰出现时都会引发一个pH下降峰，并且这种短暂的细胞酸化发生在钙峰的下游，但在锌峰的上游。我们的研究结果表明，自发、同步的锌峰是通过钙内流诱导的细胞酸化产生的，这种酸化使锌从细胞内的锌结合配体中释放出来。鉴于锌浓度的变化能够调节对突触成熟和神经元分化至关重要的蛋白质的活性，这些锌峰可能在神经元发育中起到重要的信号作用。
Zinc has been suggested to act as an intracellular signaling molecule due to its regulatory effects on numerous protein targets including enzymes, transcription factors, ion channels, neurotrophic factors and postsynaptic scaffolding proteins. However, intracellular zinc concentration is tightly maintained at steady levels under natural physiological conditions. Dynamic changes in intracellular zinc concentration have only been detected in certain types of cells that are exposed to pathologic stimuli or upon receptor ligand binding. Unlike calcium, the ubiquitous signaling metal ion that can oscillate periodically and spontaneously in various cells, spontaneous zinc oscillations have never been reported. In this work, we made the novel observation that the developing neurons generated spontaneous and synchronous zinc spikes in primary hippocampal cultures using a fluorescent zinc sensor, FluoZin-3. Blocking of glutamate receptor-dependent calcium influx depleted the zinc spikes, suggesting that these zinc spikes were driven by the glutamate-mediated spontaneous neural excitability and calcium spikes that have been characterized in early developing neurons. Simultaneous imaging of calcium or pH together with zinc, we uncovered that a downward pH spike was evoked with each zinc spike and this transient cellular acidification occurred downstream of calcium spikes, but upstream of zinc spikes. Our results suggest that spontaneous, synchronous zinc spikes were generated through calcium influx-induced cellular acidification, which liberates zinc from intracellular zinc binding ligands. Given that changes in zinc concentration can modulate activities of proteins essential for synapse maturation and neuronal differentiation, these zinc spikes might act as important signaling roles in neuronal development.
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影响因子：
2.5
作者：
Cavelier, Pauline;Attwell, David
通讯作者：
Attwell, David
影响因子：
4
作者：
Devinney, MJ;Reynolds, IJ;Dineley, KE
通讯作者：
Dineley, KE
DOI：
10.1007/bf01188497
发表时间：
1994-05-01
期刊：
JOURNAL OF NEUROCYTOLOGY
影响因子：
--
作者：
BENSON, DL;WATKINS, FH;BANKER, G
通讯作者：
BANKER, G
影响因子：
2.4
作者：
Cho YE;Lomeda RA;Ryu SH;Lee JH;Beattie JH;Kwun IS
通讯作者：
Kwun IS
影响因子：
4
作者：
Canepari, M;Mammano, F;Cherubini, E
通讯作者：
Cherubini, E