HYPEREXCITABILITY AT SITES OF NERVE INJURY DEPENDS ON VOLTAGE-SENSITIVE NA+ CHANNELS

被引:233
作者
MATZNER, O [1 ]
DEVOR, M [1 ]
机构
[1] HEBREW UNIV JERUSALEM,INST LIFE SCI,DEPT CELL & ANIM BIOL,IL-91904 JERUSALEM,ISRAEL
关键词
D O I
10.1152/jn.1994.72.1.349
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
1. We used the teased fiber method to record from single myelinated afferent axons ending in a chronic nerve injury site(neuroma) in the rat sciatic nerve or L(4,5) dorsal root. Axons were chosen for study that fired spontaneously with a stable tonic or interrupted (bursty) autorhythmic firing pattern. 2. Agents that block voltage-sensitive Na+ channels [tetrodotoxin (TTX), lidocaine], voltage-sensitive Ca2+ channels (Cd2+, Co2+, Ni2+, verapamil, D600, nifedipine, and fluarizine), voltage-sensitive K+ channels [tetraethylammonium (TEA), 4-aminopyridine (4-AP)], and Ca2+-activated K+ channels (gK(Ca2+)(+); quinidine, apamine) were applied topically to the neuroma. Effects on baseline rhythmogenesis and on the duty cycle of bursting were documented. Spike pattern analysis was used to determine whether changes in firing frequency were associated with changes in impulse initiation (electrogenesis), or resulted from (partial) block of impulse propagation downstream from the site of electrogenesis. Effects of veratridine were also noted. 3. Na+ channel blockers consistently quenched neuroma firing, and they did so by suppressing the process of impulse initiation. Only rarely was propagation block the dominant process. In bursty fibers the duration of on-periods shortened as the duration of off-periods lengthened, without a significant change in the baseline interspike interval(ISI). Veratridine accelerated firing, also via the impulse generating process. 4. Ca2+ channel blockers had essentially no effect on baseline firing rate (i.e., ISI). 5. Ca2+ channel blockers, as well as blockers of gK(Ca2+)(+), had substantial, but inconsistent effects on burst pattern. It is not clear whether this reflects variability in the experimental conditions, or heterogeneity among the fibers sampled. 6. Blockade of K+ channels failed to evoke rhythmogenesis in acutely cut axons as it does in chronically injured axons, even in the presence of veratridine. This is consistent with other evidence that ectopic neuroma firing depends on postinjury remodeling of membrane electrical properties. 7. The data indicate that, in chronically injured axons, the inward currents that underly electrogenicity, enable ectopic discharge, and, together with outward K+ currents, set the fundamental firing rhythm (ISI), operate primarily with the use of voltage-sensitive Na+ rather than Ca2+ channels. 8. The on-off duty cycle in bursty fibers was affected by Na+ channel ligands and also, although less so, and less consistently, by Ca2+ channel ligands. This indicates that both may play a role in the slow modulations of membrane potential that presumably underly interupted autorhythmicity.
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页码:349 / 359
页数:11
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