Impaired Axonal Na(+) Current by Hindlimb Unloading: Implication for Disuse Neuromuscular Atrophy.
Impaired Axonal Na(+) Current by Hindlimb Unloading: Implication for Disuse Neuromuscular Atrophy.
复制标题
轴突Na（+）电流受损，后肢卸载：对神经肌肉萎缩的影响。
DOI：
10.3389/fphys.2016.00036
复制
发表时间：
2016
影响因子：
4
通讯作者：
Kaji R
中科院分区：
文献类型：
--
作者：
Banzrai C;Nodera H;Kawarai T;Higashi S;Okada R;Mori A;Shimatani Y;Osaki Y;Kaji R
本研究旨在探讨废用性神经肌肉萎缩模型后肢去负荷（HLU）引起的外周运动轴突兴奋性变化。在正常的8周龄雄性小鼠中进行HLU，通过用连接到动物笼顶部的夹子固定近端尾部3周。通过刺激踝部坐骨神经并记录来自足部的复合肌肉动作电位（CMAP）来进行轴突兴奋性研究。卸载组的运动反应幅度为对照组幅度的51%[2.2 ± 1.3 mV（HLU）vs. 4.3 ± 1.2 mV（对照组），P = 0.03]。多轴索兴奋性分析显示，去负荷组具有较小的强度-持续时间常数（SDTC）和迟发亚兴奋性075 ± 0.01（HLU）对0.12 ± 0.01（对照），P < 0.01; 5.4 ± 1.0（HLU）对10.0 ± 1.3%（对照），P = 0.01]。从HLU释放后三周，SDTC变得与对照范围相当。使用建模研究，观察到的波形差异可以通过持续Na+电流沿着与电流泄漏相关的参数降低来解释。在HLU的坐骨神经中，编码电压门控Na+通道的SCA 1A基因的RNA的定量倾向于降低。本研究表明，轴突离子电流在体内改变HLU。功能失调的轴突离子电流是否对神经肌肉萎缩有致病作用，还是萎缩导致神经可塑性的结果，目前尚不清楚。
This study aimed to characterize the excitability changes in peripheral motor axons caused by hindlimb unloading (HLU), which is a model of disuse neuromuscular atrophy. HLU was performed in normal 8-week-old male mice by fixing the proximal tail by a clip connected to the top of the animal's cage for 3 weeks. Axonal excitability studies were performed by stimulating the sciatic nerve at the ankle and recording the compound muscle action potential (CMAP) from the foot. The amplitudes of the motor responses of the unloading group were 51% of the control amplitudes [2.2 ± 1.3 mV (HLU) vs. 4.3 ± 1.2 mV (Control), P = 0.03]. Multiple axonal excitability analysis showed that the unloading group had a smaller strength-duration time constant (SDTC) and late subexcitability (recovery cycle) than the controls [0.075 ± 0.01 (HLU) vs. 0.12 ± 0.01 (Control), P < 0.01; 5.4 ± 1.0 (HLU) vs. 10.0 ± 1.3 % (Control), P = 0.01, respectively]. Three weeks after releasing from HLU, the SDTC became comparable to the control range. Using a modeling study, the observed differences in the waveforms could be explained by reduced persistent Na+ currents along with parameters related to current leakage. Quantification of RNA of a SCA1A gene coding a voltage-gated Na+ channel tended to be decreased in the sciatic nerve in HLU. The present study suggested that axonal ion currents are altered in vivo by HLU. It is still undetermined whether the dysfunctional axonal ion currents have any pathogenicity on neuromuscular atrophy or are the results of neural plasticity by atrophy.