Increased nodal persistent Na+ currents in human neuropathy and motor neuron disease estimated by latent addition
Increased nodal persistent Na+ currents in human neuropathy and motor neuron disease estimated by latent addition
复制标题
DOI：
10.1016/j.clinph.2006.07.309
复制
发表时间：
2006-11
影响因子：
4.7
通讯作者：
N. Tamura;S. Kuwabara;S. Misawa;K. Kanai;M. Nakata;S. Sawai;T. Hattori
中科院分区：
文献类型：
--
作者：
N. Tamura;S. Kuwabara;S. Misawa;K. Kanai;M. Nakata;S. Sawai;T. Hattori
目的研究人神经病和运动神经元病时结持续性Na+电流的变化。在人类运动神经元轴突中，约有1.0%的Na+通道在静息状态下是活跃的，被称为“持久性”Na+通道，其电导可以通过体内潜伏增加技术进行无创性估计。（LMND; n=19）或肌萎缩侧索硬化症（ALS; n=36）和27名年龄匹配的正常受试者。短暂的超极化条件电流脉冲，并在0.2ms的条件测试间隔的阈值变化作为持续性Na+电流的大小的估计。阈值电张力和超常性也被测量为静息膜电位的指标。在神经病或LMND患者中，0.2ms阈值变化显著大于正常对照组（p<0.05），并且在ALS患者中倾向于大于正常对照组（p=0.075）。阈值电紧张和超常在每个患者组和正常对照组中没有差异，表明患者的膜电位没有改变。在轴突神经病变的恢复阶段，阈值变化增加与复合肌肉动作电位振幅的增加平行。可能与轴突再生或侧枝发芽或Na+变化有关轴突兴奋性增加可能是下运动神经元常见的阳性运动症状如肌肉痉挛的部分原因紊乱
OBJECTIVETo investigate the changes in nodal persistent Na+currents in human neuropathy and motor neuron disease. In human motor axons, approximately 1.0% of total Na+channels are active at rest, termed “persistent” Na+channels, and the conductance can be non-invasively estimated by the technique of latent addition in vivo.METHODSLatent addition was performed in median motor axons of 93 patients with axonal neuropathy (n=38), lower motor neuron disorder (LMND; n=19) or amyotrophic lateral sclerosis (ALS; n=36) and in 27 age-matched normal subjects. Brief hyperpolarizing conditioning current pulses were delivered, and threshold change at the conditioning-test interval of 0.2ms was measured as an estimator of the magnitude of persistent Na+currents. Threshold electrotonus and supernormality were also measured as indicators of resting membrane potential.RESULTSThreshold changes at 0.2ms were significantly greater in patients with neuropathy or LMND (p<0.05), and tended to be greater in ALS patients (p=0.075) than in normal controls. Threshold electrotonus and supernormality did not differ in each patient group and normal controls, suggesting that membrane potential is not altered in patients. In the recovery phase of axonal neuropathy, the threshold changes increased in parallel with an increase in amplitudes of compound muscle action potential.CONCLUSIONSPersistent Na+currents appear to increase commonly in disorders involving lower motor neurons, possibly associated with axonal regeneration or collateral sprouting or changes in Na+channel gating.SIGNIFICANCEThe increased axonal excitability could partly be responsible for positive motor symptoms such as muscle cramping frequently seen in lower motor neuron disorders.