Misawa Sonoko, Kuwabara Satoshi, Kanai Kazuaki, Tamura Noriko, Nakata Miho, Ogawara Kazue, Yagui Kazuo, Hattori Takamichi
Department of Neurology, Chiba University School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Clin Neurophysiol. 2006 Apr;117(4):815-20. doi: 10.1016/j.clinph.2005.11.019. Epub 2006 Feb 21.
To investigate the effects of hyperglycemia on persistent Na+ currents in human diabetic nerves, eliminating the factors of passive membrane properties as a factor. Previous studies show that strength-duration time constant of a nerve is shortened under hyperglycemia, suggesting reduced axonal persistent Na+ currents. However, the time constant is also affected by changes in passive membrane properties. Latent addition using computerized threshold tracking is a new method that can separately evaluate Na+ currents and passive membrane properties.
Latent addition was used to estimate nodal Na+ currents in median motor axons of 83 diabetic patients. Brief hyperpolarizing conditioning current pulses were delivered, and threshold changes at the conditioning-test interval of 0.2 ms were measured as an indicator of nodal persistent Na+ currents. Seventeen patients were examined before and after insulin treatment.
There was an inverse linear relationship between hemoglobin A1c levels and threshold changes at 0.2 ms (P=0.02); the higher hemoglobin A1c levels were associated with smaller threshold changes. After insulin treatment, there was a significant improvement in nerve conduction velocities associated with greater threshold changes at 0.2 ms (P=0.03), suggesting an increase in persistent Na+ currents. The fast component of latent addition, an indicator of passive membrane properties, was not affected by the state of glycemic control.
Hyperglycemia could suppress nodal persistent Na+ currents, presumably because of reduced trans-axonal Na+ gradient or impaired Na+ channels, and this can be rapidly restored by glycemic control.
Reduced nodal Na+ currents may partly contribute to the pathophysiology of human diabetic neuropathy.
研究高血糖对人糖尿病神经中持续性钠电流的影响，排除被动膜特性因素。先前的研究表明，在高血糖状态下神经的强度-时间常数缩短，提示轴突持续性钠电流减少。然而，该时间常数也受被动膜特性变化的影响。使用计算机化阈值跟踪的潜在叠加法是一种可分别评估钠电流和被动膜特性的新方法。
采用潜在叠加法估计83例糖尿病患者正中运动轴突的结区钠电流。施加短暂的超极化调节电流脉冲，并测量0.2毫秒调节-测试间隔时的阈值变化，作为结区持续性钠电流的指标。17例患者在胰岛素治疗前后接受检查。
糖化血红蛋白水平与0.2毫秒时的阈值变化呈负线性关系（P=0.02）；糖化血红蛋白水平越高，阈值变化越小。胰岛素治疗后，神经传导速度显著改善，同时0.2毫秒时的阈值变化更大（P=0.03），提示持续性钠电流增加。潜在叠加的快速成分，即被动膜特性的指标，不受血糖控制状态的影响。
高血糖可能抑制结区持续性钠电流，推测是由于跨轴突钠梯度降低或钠通道受损，而血糖控制可使其迅速恢复。
结区钠电流减少可能部分导致人类糖尿病神经病变的病理生理过程。
