Augmentation by 4-aminopyridine of vestibulospinal free fall responses in chronic spinal-injured cats

This study examines the effect of the potassium channel blocker 4-aminopyridine (4-AP) on free fall responses (FFR) in the hindlimb muscles of chronically spinal injured cats. The thoracic spinal cord of 7 adult female cats was injured by a standardized contusion method. At 3-7 months post-injury the FFR in 6 hindlimb muscles was recorded electromyographically in each animal, under ketamine sedation. The normal short-latency response to a sudden drop was severely attenuated in all injured animals and practically undetectable in 2 cases. Within 15 min following intravenous administration of 1 mg/kg 4-AP, there was profound augmentation of the amplitude of the FFR and a tendency toward normalization of latency in all animals, though the normal amplitude range was not attained. The same 4-AP dose produced a relatively small increase of FFR amplitude in only 2 of 4 normal, uninjured animals tested. The data are consistent with previous observations that low doses of 4-AP restore conduction in some critically demyelinated axons, and provide support for the hypothesis that conduction block in surviving axons is responsible for a proportion of the dysfunction in chronic spinal injury. Augmentation of FFR in injured animals may also result partly from increased transmitter release in both spinal cord and periphery, due to the presynaptic effects of 4-AP.