The effects of hyperglycaemic hypoxia (a condition possibly involved in the pathogenesis of diabetic neuropathy) on the depolarizing after-potential and the potassium conductance of myelinated rat spinal root axons were investigated using electrophysiological recordings from intact spinal roots and from excised, inside-out axonal membrane patches. 2. Isolated spinal roots were exposed to hypoxia in solutions containing normal or high glucose concentrations. The depolarizing after-potential of compound action potentials was only enhanced in spinal roots exposed to hyperglycaemic (25 mM D-glucose) hypoxia. A maximal effect was seen in bathing solutions with low buffering power. 3. The depolarizing after-potential was also enhanced by cytoplasmic acidification after replacement of 10-30 mM chloride in the bathing solution by propionate. 4. Multi-channel current recordings from excised, inside-out axonal membrane patches were used to study the effects of cytoplasmic acidification on voltage-dependent K+ conductances with fast (F channels) and intermediate (I channels) kinetics of deactivation. 5. F channels were blocked by small changes in cytoplasmic pH (50% inhibition at pH 6.9). I channels were much less sensitive to intra-axonal acidification. 6. In conclusion, our data show that hyperglycaemic hypoxia enhances the depolarizing after-potential in peripheral rat axons. The underlying mechanism seems to be an inhibition of a fast, voltage-dependent axonal K+ conductance by cytoplasmic acidification. This alteration in membrane conductance may contribute to positive symptoms in diabetic neuropathy.
摘要
利用完整脊髓神经根和分离的、内面向外的轴突膜片进行电生理记录，研究了高血糖性缺氧（一种可能参与糖尿病性神经病变发病机制的状况）对大鼠有髓脊髓神经根轴突去极化后电位和钾电导的影响。2. 将分离的脊髓神经根置于含有正常或高葡萄糖浓度的溶液中进行缺氧处理。复合动作电位的去极化后电位仅在暴露于高血糖（25 mM D -葡萄糖）性缺氧的脊髓神经根中增强。在缓冲能力低的浴液中观察到最大效应。3. 用丙酸盐替代浴液中10 - 30 mM的氯离子后，细胞质酸化也增强了去极化后电位。4. 从分离的、内面向外的轴突膜片进行多通道电流记录，以研究细胞质酸化对具有快速（F通道）和中间（I通道）失活动力学的电压依赖性K +电导的影响。5. F通道被细胞质pH的微小变化所阻断（在pH 6.9时50%抑制）。I通道对轴突内酸化的敏感性要低得多。6. 总之，我们的数据表明，高血糖性缺氧增强了大鼠外周轴突的去极化后电位。潜在机制似乎是细胞质酸化抑制了快速的、电压依赖性轴突K +电导。这种膜电导的改变可能导致糖尿病性神经病变的阳性症状。
