FHF-independent conduction of action potentials along the leak-resistant cerebellar granule cell axon.

FHF-independent conduction of action potentials along the leak-resistant cerebellar granule cell axon.
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DOI:
10.1038/ncomms12895
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发表时间:
2016-09-26
影响因子:
16.6
通讯作者:
Goldfarb, Mitchell
Goldfarb, Mitchell
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Dover, Katarzyna;Marra, Christopher;Solinas, Sergio;Popovic, Marko;Subramaniyam, Sathyaa;Zecevic, Dejan;D'Angelo, Egidio;Goldfarb, Mitchell

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脊椎动物中枢神经系统中的神经元在不同的亚细胞区室中启动和传导钠动作电位,所述亚细胞区室在结构和电学上不同。在这里,我们报告了几个意想不到的被动和主动特性的小脑颗粒细胞的无髓轴突。而在轴突起始段的尖峰起始依赖于钠通道(Nav)相关的成纤维细胞生长因子同源因子(FHF)蛋白来延迟Nav失活,远端轴突Nav显示很少的FHF关联或FHF要求高频传输,速度和波形的传导动作电位。此外,沿远端轴突的漏导密度估计为体树突膜的漏导密度的沿着<1%。无FHF Navs的更快失活速率与非常低的轴突漏导一起用于最小化重复尖峰传导期间和静息时的离子通量和能量需求。在中枢神经系统中,在Ranvier结处的Navs不存在FHF,这表明沿着有髓轴突的电流通量最小化的类似机制。 已知FHF调节电压门控钠通道(NaV)。在这里,作者比较了FHF在小脑颗粒细胞增殖中的作用,并发现NaV在远端轴突功能中独立于FHF,允许更快的失活速率并减少重复尖峰期间的能量需求。
Neurons in vertebrate central nervous systems initiate and conduct sodium action potentials in distinct subcellular compartments that differ architecturally and electrically. Here, we report several unanticipated passive and active properties of the cerebellar granule cell's unmyelinated axon. Whereas spike initiation at the axon initial segment relies on sodium channel (Nav)-associated fibroblast growth factor homologous factor (FHF) proteins to delay Nav inactivation, distal axonal Navs show little FHF association or FHF requirement for high-frequency transmission, velocity and waveforms of conducting action potentials. In addition, leak conductance density along the distal axon is estimated as <1% that of somatodendritic membrane. The faster inactivation rate of FHF-free Navs together with very low axonal leak conductance serves to minimize ionic fluxes and energetic demand during repetitive spike conduction and at rest. The absence of FHFs from Navs at nodes of Ranvier in the central nervous system suggests a similar mechanism of current flux minimization along myelinated axons. FHFs are known to regulate voltage-gated sodium channels (NaVs). Here, the authors compare the role of FHFs in cerebellar granule cell propagation, and find NaVs in the distal axon function independently of FHFs, allowing for faster inactivation rates and reducing energy demands during repetitive spiking.
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