Du Zhengqing, Meng Ziqiang
Shanxi University of Finance & Economics, Taiyuan 030006, PR China.
Neurosci Lett. 2006 Sep 11;405(1-2):147-52. doi: 10.1016/j.neulet.2006.06.046. Epub 2006 Jul 20.
This study addressed the effect of sulfur dioxide (SO(2)) derivatives on high-voltage-activated calcium currents (HVA-I(Ca)) in somatic membrane of freshly isolated rat dorsal root ganglion (DRG) neurons by using the whole-cell configuration of patch-clamp technique. High-threshold Ca(2+) channels are highly expressed in small dorsal root ganglion neurons. SO(2) derivatives increased the amplitudes of calcium currents in a concentration-dependent and voltage-dependent manner. The 50% enhancement concentrations (EC(50)) of SO(2) derivatives on HVA-I(Ca) was about 0.4 microM. In addition, SO(2) derivatives significantly shifted the activation and inactivation curve in the depolarizing direction. Parameters for the fit of a Boltzmann equation to mean values for the activation were V(1/2)=-17.9+/-1.3 mV before and -12.5+/-1.1 mV after application 0.5 microM SO(2) derivatives 2 min (P<0.05). The half inactivation of HVA-I(Ca) was shifted 9.7 mV to positive direction (P<0.05). Furthermore, SO(2) derivatives significantly prolonged the slow constant of inactivation, slowed the fast recovery but markedly accelerated the slow recovery of HVA-I(Ca) from inactivation. From HP of -60 mV 0.5 microM SO(2) derivatives increased the amplitude of HVA-I(Ca) with a depolarizing voltage step to -10 mV about 54.0% in small DRG neurons but 33.3% in large DRG neurons. These results indicated a possible correlation between the change of calcium channels and SO(2) inhalation toxicity, which might cause periphery neurons abnormal regulation of nociceptive transmission via calcium channels.
本研究采用膜片钳技术的全细胞记录模式,探讨了二氧化硫(SO₂)衍生物对新鲜分离的大鼠背根神经节(DRG)神经元胞体膜上高电压激活钙电流(HVA-I(Ca))的影响。高阈值Ca²⁺通道在小直径背根神经节神经元中高度表达。SO₂衍生物以浓度依赖性和电压依赖性方式增加钙电流幅度。SO₂衍生物对HVA-I(Ca)的半数增强浓度(EC₅₀)约为0.4 μM。此外,SO₂衍生物使激活曲线和失活曲线显著向去极化方向移动。用玻尔兹曼方程拟合激活平均值的参数,在应用0.5 μM SO₂衍生物2分钟前,V(1/2)= -17.9 ± 1.3 mV,应用后为 -12.5 ± 1.1 mV(P<0.05)。HVA-I(Ca)的半数失活向正向移动9.7 mV(P<0.05)。此外,SO₂衍生物显著延长了失活的慢时间常数,减慢了快速恢复,但显著加速了HVA-I(Ca)从失活状态的慢速恢复。从小直径DRG神经元 -60 mV的静息电位开始,0.5 μM SO₂衍生物使去极化电压阶跃至 -10 mV时HVA-I(Ca)的幅度增加约54.0%,而大直径DRG神经元增加33.3%。这些结果表明钙通道变化与SO₂吸入毒性之间可能存在关联,这可能导致外周神经元通过钙通道对伤害性传入信号的调节异常。