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瞬时外向钾电流的降低介导了慢性压迫背根神经节细胞兴奋性的升高

晏妮, 李潇寒, 程祺, 严进, 倪鑫, 孙继虎

第二军医大学生理学教研室.上海 200433；第二军医大学心理学教研室.上海 200433

摘要

慢性压迫大鼠背根神经节(chronic compression of the dorsal root,ganglion,CCD)后,背根神经节细胞兴奋性升高,但引起神经元兴奋性改变的离子通道机制还需进一步探索。该实验采用胞内记录以及全细胞膜片钳记录方法,研究急性分离的大鼠背根神经节细胞兴奋性改变与瞬时外向钾电流(A--type potassium current,Ⅰ_(A))的关系。结果表明,CCD术后背根神经节细胞兴奋性升高,在急性分离的体外细胞中仍继续存在,表现为对辣椒素敏感的背根神经节细胞产生动作电位的最小电流刺激强度,即阈电流(current threshold)及阈电位(voltage threshold)降低;给予正常对照组神经元(未压迫损伤)瞬时外向钾通道阻断剂4--氨基吡啶,出现了类似CCD术后兴奋性升高的改变。进一步用两步电压钳方法分离Ⅰ_(A),研究CCD术后神经元Ⅰ_(A)的变化,结果表明,CCD组神经元的Ⅰ_(A)比对照组神经元Ⅰ_(A)降低,并且与其阈电位的改变一致。以上结果提示,背根神经节压迫受损后,神经节细胞Ⅰ_(A)降低可能参与介导了神经节细胞兴奋性的升高。

关键词： 钾通道; 背根神经节; 兴奋性; 痛

Decreased A--type potassium current mediates the hyperexcitability of nociceptive neurons in the chronically compressed dorsal root ganglia

Yan Ni, Li Xiaohan, Cheng Qi, Yan Jin, Ni Xin, Sun Jihu

Department of Physiology,Department of Psychology,the Second Military Medical University.Shanghai 200433

Abstract

The excitability of nociceptive neurons increases in the intact dorsal root ganglion (DRG) after a chronic compression, but the underlying mechanisms are still unclear. The aim of this study was to investigate the ionic mechanisms underlying the hyperexcit-ability of nociceptive neurons in the compressed ganglion. Chronic compression of DRG (CCD) was produced in adult rats by inserting two rods through the intervertebral foramina to compress the L4 DRG and the ipsilateral L5 DRG. After 5-7 d, DRG somata were dissociated and placed in culture for 12-18 h. In sharp electrode recording model, we examined the lower current threshold and the depolarized membrane potential in the acutely dissociated CCD neurons, which are indication of hyperexcitability that is intrinsic to the soma. Since voltage-gated K~(+) (Kv) channels in primary sensory neurons are important for regulation of neuronal excitability, we hypothesized that CCD would alter K~(+) current properties in primary sensory neurons. We examined the effects of 4-aminopyridine (4-AP), a specific antagonist of A-type potassium channel, on the excitability of the control DRG neurons. With 4-AP in the external solution, the control DRG neurons depolarized (with discharges in some cells) and decreased their current threshold as the CCD neurons demonstrated, indicating the involvement of decreased A-type potassium current in the hyperexcitability of the injured neurons. Furthermore, the alteration of A-type potassium current in nociceptive neurons in the compressed ganglion was investigated with the whole-cell patch-clamp recording model. CCD significantly decreased A-type potassium current density in nociceptive DRG neurons. These data suggest that a reduction in A-type potassium currents contributes, at least in part, to the increase in neuron excitability that may lead to the development of pain and hyperalgesia associated with CCD.

Key words: Potassium channel;Dorsal root ganglion;Excitability;pain

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引用本文：

晏妮, 李潇寒, 程祺, 严进, 倪鑫, 孙继虎. 瞬时外向钾电流的降低介导了慢性压迫背根神经节细胞兴奋性的升高[J]. 生理学报 2007; 59 (2): 240-246.

Yan Ni, Li Xiaohan, Cheng Qi, Yan Jin, Ni Xin, Sun Jihu. Decreased A--type potassium current mediates the hyperexcitability of nociceptive neurons in the chronically compressed dorsal root ganglia. Acta Physiol Sin 2007; 59 (2): 240-246 (in Chinese with English abstract).