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

小背根神经节神经元优先表达Na^+通道异构体Na_γ1.9，介导河豚毒素抗性（fix -r） Na^+电流。利用全细胞膜片钳记录技术研究了na_γ - 1.9 （I_<NN>）介导的Na^+电流的性质。为了从含有Na_γ1.8介导的另一种类型的TIX-R Na^+电流的异质TIX-R Na^+电流中分离出I_<NN>，我们使用Na_γ1.8-null突变小鼠。在膜片移液液中以F作为内阴离子时，I_<NN>的激活和失活动力学均随时间向超极化方向移动。当Cl^-作为内部阴离子时，没有观察到这种随时间变化的动力学。函数表达式。na_ <NN>在细胞分离后随时间下降，在培养过程中恢复，表明na_γ - 1.9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。在全细胞记录中，在可变延迟后，INaN的峰值幅度急剧增加，就好像不活跃或沉默的通道被“点燃”一样。如此不寻常的幅度增加可能。通过在移液管溶液中加入AIP或用制氨抑素穿孔膜片钳技术记录来防止，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Na^+通道的可塑性提供了一种见解，这种可塑性与Na^+通道伴随异常疼痛状态的病理功能有关。

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.