Nodal persistent Na⁺ currents in human diabetic nerves estimated by the technique of latent addition

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• 作者：Sonoko Misawa ; Satoshi Kuwabara ; Kazuaki Kanai ; Noriko Tamura ; Miho Nakata ; Kazue Ogawara ; Kazuo Yagui and Takamichi Hattori
• 刊名：Clinical Neurophysiology
• 出版年：2006
• 出版时间：April 2006
• 年：2006
• 卷：117
• 期：4
• 页码：815-820
• 全文大小：151 K

文摘

Objective

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.

Methods

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.

Results

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.

Conclusions

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.

Significance

Reduced nodal Na⁺ currents may partly contribute to the pathophysiology of human diabetic neuropathy.