Mg. Fehlings et R. Nashmi, CHANGES IN PHARMACOLOGICAL SENSITIVITY OF THE SPINAL-CORD TO POTASSIUM CHANNEL BLOCKERS FOLLOWING ACUTE SPINAL-CORD INJURY, Brain research, 736(1-2), 1996, pp. 135-145
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.