Slow sodium-dependent potential oscillations contribute to ectopic firing in mammalian demyelinated axons
Slow sodium-dependent potential oscillations contribute to ectopic firing in mammalian demyelinated axons
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DOI：
10.1093/brain/120.4.647
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发表时间：
1997-04-01
期刊：
影响因子：
14.5
通讯作者：
Smith, KJ
中科院分区：
文献类型：
--
作者：
Kapoor, R;Li, YG;Smith, KJ
异位动作电位可以在轴突脱髓鞘的区域产生，并且被认为有助于患有脱髓鞘病症（诸如多发性硬化症）的患者的一系列症状。异位冲动产生的机制尚不确定。我们以前已经表明，这种异位活动可以导致内向钾电流。钾通道阻断剂4-氨基吡啶（4-aminopyridine，4AP）有时会引起脱髓鞘病变的异位活动。为了研究这种现象，我们已经在脱髓鞘轴突的异位活动的轴突内记录，在存在和不存在5 mM 4AP。4AP促进了一种放电模式，这种模式在没有这种药物的情况下也在脱髓鞘轴突中观察到，尽管不太频繁，即单脉冲序列或短脉冲的高频脉冲序列。当记录接近脱髓鞘病变，冲动产生的基础，几乎正弦振荡的膜电位。这种振荡被钠通道阻断剂河豚毒素（0.1-1 μ M）消除。我们的结论是，异位尖峰引起的4AP产生的膜电位振荡与脱髓鞘的网站。这些振荡的钠依赖性电流，连同我们先前描述的长期内向钾电流，可能有助于产生异位放电的一系列疾病的有髓轴突。
Ectopic action potentials can arise at regions of axonal demyelination, and are believed to contribute to a range of symptoms in patients with demyelinating conditions such as multiple sclerosis. The mechanism(s) by which the ectopic impulses are generated are uncertain. We have previously shown that such ectopic activity can result from inward potassium currents. Paradoxically, the potassium channel blocking agent 4-aminopyridine (4AP) can sometimes cause ectopic activity in demyelinating lesions. To study this phenomenon we have made intra-axonal recordings of ectopic activity in demyelinated axons, both in the presence and absence of 5 mM 4AP. 4AP promoted a pattern of firing which was also observed, albeit less frequently, in demyelinated axons in the absence of this drug, namely trains of single impulses, or trains of short, high-frequency bursts of impulses. When recorded close to the demyelinated lesion, the impulses were generated by an underlying, almost sinusoidal oscillation of the membrane potential. This oscillation was abolished by the sodium channel blocking agent tetrodotoxin (0.1-1 mu M). We conclude that the ectopic spiking induced by 4AP is generated by membrane potential oscillations associated with the site of demyelination. The sodium-dependent current underlying these oscillations, together with the prolonged inward potassium currents which we have previously described, may contribute to the generation of ectopic discharges in a range of disorders of myelinated axons.