The effects of 4-aminopyridine on the spinal cord: rhythmic discharges recorded from the peripheral nerves

The effects of an intravenous injection (20 mg/kg) of 4-aminopyridine (4-AP) were initially investigated in acute low spinal cats (Th 13), in which L-DOPA had induced fictive locomotion after paralysis. 4-AP first accelerated the locomotor rhythm and could also change markedly the pattern of activation of some muscle nerves. Shortly after, the locomotor activity was replaced by synchronous rhythmic discharges (2.5-8.5 Hz) in flexor and extensor muscle nerves of the same limb girdle. Similar rhythmic activity was recorded after 4-AP alone (5-20 mg/kg) in the acute decerebrate spinal cat. Whilst the mean rate of the rhythmic activity could differ in the two limb girdles, discharges generated in one girdle appeared to be strongly influenced by those generated in the other. After a complete section of the spinal cord (Th13), the activity persisted in both the rostral and caudal segments although the interactions between the two disappeared. The persistence of the rhythmic activity caudal to the section underscores its spinal origin. In the chronic spinal rat, such rhythmic activity could still be induced in the lumbo-sacral cord despite degeneration of descending pathways. It appears that large doses of 4-AP exert potent effects on the spinal cord which can override other patterns of activity and synchronize the electrical activity of many neuronal elements.