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 sensit ivity of dorsal column white matter to a variety of K+ channel blocker s, including 4-aminopyridine (4-AP), following acute spinal cord injur y (SCI) in vitro using a modified aneurysm clip. Compound action poten tials (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 un injured controls as early as 10 min following injury. Microelectrode d erived field potential recordings showed a significantly greater incre ase 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 recordin gs 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 am plitude with 4-AP was even more pronounced (P < 0.05) at higher temper atures (37 degrees C). As shown by sucrose gap, 4-AP also caused a del ay in repolarization of the CAP and depolarization of the resting memb rane potential of acutely injured axons. TEA (0.1 mM and 10 mM), when infused alone and with CsCl (10 mM), produced similar effects on injur ed 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 caus es axonal dysfunction partly due to abnormal activation of 4-AP-sensit ive 'fast' K+ channels.