Shi R, Kelly T M, Blight A R
Division of Neurosurgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Exp Neurol. 1997 Dec;148(2):495-501. doi: 10.1006/exnr.1997.6706.
The effect of the potassium channel blocker, 4-aminopyridine (4-AP), on conduction of action potentials in injured guinea pig spinal cord axons was measured using isolated tracts in oxygenated Krebs' solution at 37 degrees C. The dose-response characteristics of acutely and chronically injured axons were compared. The maximal improvement of conduction occurred in acutely injured axons at a concentration of 100 microM 4-AP, but in chronically injured spinal cord at 10 microM. The threshold for significant response to 4-AP was between 0.5 and 1 microM in chronically injured cords, and between 1 and 10 microM following acute compression injury. The difference in susceptibility to potassium channel blockade may be related to underlying differences in the mechanism of conduction block at the two stages of injury. Initially, junctions between axons and myelin are acutely disrupted, altering primarily the leakage resistance of the myelin sheath and periaxonal space. In chronically injured cords, there is widespread but incomplete process of repair in the lesion site, which leaves many axons partially myelinated. The difference in sensitivity to 4-AP suggests there is also some modification of the accessibility of axonal potassium channel or a change in their affinity for the drug.
在37℃的含氧 Krebs 溶液中，使用分离的神经束测量钾通道阻滞剂4-氨基吡啶（4-AP）对豚鼠脊髓损伤轴突动作电位传导的影响。比较了急性和慢性损伤轴突的剂量反应特征。在急性损伤轴突中，100 microM 的4-AP 浓度时传导改善最大，而在慢性损伤脊髓中，10 microM 时传导改善最大。在慢性损伤脊髓中，对4-AP 产生显著反应的阈值在0.5至1 microM 之间，急性压迫损伤后在1至10 microM 之间。对钾通道阻断敏感性的差异可能与损伤两个阶段传导阻滞机制的潜在差异有关。最初，轴突与髓鞘之间的连接急性中断，主要改变髓鞘和轴突周围间隙的漏电电阻。在慢性损伤脊髓中，损伤部位存在广泛但不完全的修复过程，许多轴突部分髓鞘化。对4-AP 敏感性的差异表明，轴突钾通道的可及性也有一些改变，或者其对药物的亲和力发生了变化。
