Conduction block in acute and chronic spinal cord injury: different dose-response characteristics for reversal by 4-aminopyridine.
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.
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Division of Neurosurgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Kelly
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Blight
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D015761:4-Aminopyridine / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects*; D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D013119:Spinal Cord Injuries / Q000503:physiopathology*
D015761:4-Aminopyridine