Changes in pharmacological sensitivity of the spinal cord to potassium channel blockers following acute spinal cord injury.

In this investigation we studied changes in the pharmacological sensitivity of dorsal column white matter to a variety of K+ channel blockers, including 4-aminopyridine (4-AP), following acute spinal cord injury (SCI) in vitro using a modified aneurysm clip. Compound action potentials (CAPs) were recorded extracellularly with microelectrodes and by the sucrose gap recording technique. With acute trauma, injured axons showed significantly enhanced sensitivity to 4-AP in comparison to uninjured controls as early as 10 min following injury. Microelectrode derived field potential recordings showed a significantly greater increase in a delayed positive component (P2) of the CAP at both 1 and 5 mM 4-AP in injured as compared to noninjured axons. Sucrose gap recordings showed an increase in CAP area and amplitude of injured axons with 1 mM 4-AP at 22 degrees C. The relative improvement in CAP area and amplitude with 4-AP was even more pronounced (P < 0.05) at higher temperatures (37 degrees C). As shown by sucrose gap, 4-AP also caused a delay in repolarization of the CAP and depolarization of the resting membrane potential of acutely injured axons. TEA (0.1 mM and 10 mM), when infused alone and with CsCl (10 mM), produced similar effects on injured and intact axons. In conclusion, the results of this study show an altered sensitivity of the spinal cord to 4-AP following acute SCI. In contrast, TEA and CsCl exhibit no difference in their effects on low frequency axonal conduction between injured and noninjured axons. The data suggest that acute traumatic myelin disruption following SCI causes axonal dysfunction partly due to abnormal activation of 4-AP-sensitive 'fast' K+ channels.