Identification of Persistent and Resurgent Sodium Currents in Spiral Ganglion Neurons Cultured from the Mouse Cochlea.
Identification of Persistent and Resurgent Sodium Currents in Spiral Ganglion Neurons Cultured from the Mouse Cochlea.
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DOI：
10.1523/eneuro.0303-17.2017
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发表时间：
2017-11
期刊：
影响因子：
3.4
通讯作者：
Jagger DJ
中科院分区：
文献类型：
--
作者：
Browne L;Smith KE;Jagger DJ
在螺旋神经节神经元（sgn）中，听觉神经的传入单元，高自发和诱发放电率确保了描述传入声音关键特征的时间代码的保存。在出生后的发育过程中，离子通道亚型的时空分布有助于sgn动作电位产生的成熟，并有助于它们根据快速变化的输入产生spike模式的能力。在这里，我们描述了从小鼠培养的sgn中对河豚毒素（TTX）敏感的Na+电流，其特性可能支持这种快速尖峰行为。阈下持续Na+电流（INaP）和恢复Na+电流（INaR）均在听力开始前出现，并随着听力成熟而变得更加普遍。Navβ4亚单位被认为在神经系统其他部位介导INaR中发挥关键作用，被免疫定位到听神经中产生尖峰的第一半球和Ranvier周围淋巴结。ATX-II是一种海葵毒素，可以选择性地减缓经典的Na+通道失活，在电压钳记录中使INaP增强5倍，使INaR增强3倍。在电流箝位下快速适应的sgn中，ATX-II增加了激发额外动作电位的可能性。这些数据表明INaP和INaR是sgn兴奋性的新调节器，并且与它们在其他神经元类型中的作用一致，我们认为这些非经典Na+电流可能有助于控制听神经的难阻性。
In spiral ganglion neurons (SGNs), the afferent single units of the auditory nerve, high spontaneous and evoked firing rates ensure preservation of the temporal code describing the key features of incoming sound. During postnatal development, the spatiotemporal distribution of ion channel subtypes contributes to the maturation of action potential generation in SGNs, and to their ability to generate spike patterns that follow rapidly changing inputs. Here we describe tetrodotoxin (TTX)-sensitive Na+ currents in SGNs cultured from mice, whose properties may support this fast spiking behavior. A subthreshold persistent Na+ current (INaP) and a resurgent Na+ current (INaR) both emerged prior to the onset of hearing and became more prevalent as hearing matured. Navβ4 subunits, which are proposed to play a key role in mediating INaR elsewhere in the nervous system, were immunolocalized to the first heminode where spikes are generated in the auditory nerve, and to perisomatic nodes of Ranvier. ATX-II, a sea anemone toxin that slows classical Na+ channel inactivation selectively, enhanced INaP five-fold and INaR three-fold in voltage clamp recordings. In rapidly-adapting SGNs under current clamp, ATX-II increased the likelihood of firing additional action potentials. The data identify INaP and INaR as novel regulators of excitability in SGNs, and consistent with their roles in other neuronal types, we suggest that these nonclassical Na+ currents may contribute to the control of refractoriness in the auditory nerve.