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Functional role of the voltage-gated sodium charnel in chronic pain state

电压门控钠通道在慢性疼痛状态中的功能作用

基本信息

批准号：
18613008
负责人：
OGATA Nobukuni
金额：
$ 2.45万
依托单位：
Hiroshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18613008/
关键词：
chronic pain sodium channel primary sensory neuron

项目摘要

Small dorsal root ganglion neurons express preferentially the Na^+ channel isoform Na_γ1.9 that mediates a tetrodotoxin-resistant (TIX-R) Na^+ current. We investigated properties of the Na^+ current mediated by Na_γ1.9 (I_<NN>) using the whole-cell, patch-clamp recording technique. To isolate I_<NN> from heterogeneous TIX-R Na^+ currents that also contain another type of TIX-R Na^+ current mediated by Na_γ1.8, we used Na_γ1.8-null mutant mice. When F was used as an internal anion in the patch pipette solution, both the activation and inactivation kinetics for I_<NN> shifted in the hyperpolarizing direction with time. Such a time-dependent shift of the kinetics was not observed when Cl^- was used as an internal anion. Functional expression. Of I_<NN> declined with time after cell dissociation and recovered during culture, implying that Na_γ1.9 may be regulated dynamically by trophic factors or depend on subtle environmental factors for its survival. During whole-cell recordings, the peak amplitude of INaN increased dramatically after a variable delay, as if inactive or silent channels had been "kindled". Such an unusual increase of the amplitude could.be prevented by adding AIP to the pipette solution or by recording with the nystatin-perforated patch-clamp technique, suggesting that the rupture of patch membrane affected the behaviour of NaV1.9. These peculiar properties of INaN may provide an insight into the plasticity of Na^+ charnels that are related to pathological functions of Na^+ channels accompanying abnormal pain states.

小的背根神经节神经元优先表达Na^+通道亚型Na_γ1.9，它介导河豚毒素抗性（TIX-R）Na^+电流。我们用全细胞膜片钳技术研究了Na_γ1.9（I_）介导的Na^+电流的特性<NN>。为了<NN>从不均一的TIX-R Na^+电流中分离出I_，我们使用了Na_γ 1.8缺失突变小鼠，这些不均一的TIX-R Na^+电流中还含有Na_γ 1.8介导的另一种TIX-R Na^+电流。当F被用作贴片移液器溶液中的内部阴离子时，I_的激活和失活动力学均<NN>随时间向超极化方向移动。当Cl^-被用作内阴离子时，没有观察到这种随时间变化的动力学变化。功能性表达。Na<NN>_γ1.9在细胞分离后随时间的延长而下降，在培养过程中恢复，提示Na_γ1.9的存活可能受营养因子的动态调节或依赖于微妙的环境因子。在全细胞记录过程中，INaN的峰值幅度在可变延迟后急剧增加，就好像不活跃或沉默的通道被“点燃”一样。这种不寻常的幅度增加could.be通过向移液器溶液中加入AIP或通过用制霉菌素穿孔膜片钳技术记录来防止，这表明膜片膜的破裂影响了NaV1.9的行为。INaN的这些特殊性质可能为了解Na^+通道的可塑性提供了新的思路，而Na^+通道的可塑性与伴随异常疼痛状态的Na^+通道的病理功能有关。