阻断Nav1.8通道对右侧星状神经节的影响

Effects of blocking Nav1.8 channels on the right stellate ganglia

目的研究利用电压门控钠离子通道1.8(Nav1.8)特异性阻断剂A-803467局部阻断Nav1.8对右侧星状神经节(RSG)的影响。方法 24只成年家犬随机分为对照组(DMSO)、低浓度组、中浓度组和高浓度组,每组6只,向RSG内局部分别注射0.1 m L DMSO和低(10 mmol/L)、中(15 mmol/L)、高浓度(20 mmol/L)的A-803467,并在注射前和注射后30 min测定由高频刺激RSG引起的最大心率的变化情况和RSG的神经活性频率和振幅变化情况。以刺激电压为横坐标,心率变化的最大百分比为纵坐标绘制出的电压-心率反应曲线以反映RSG的功能情况。结果在基础状态时,对照组和低、中、高浓度组的RSG功能和神经活性比较,差异均无统计学意义(P>0.05);在注射A-803467后30 min,可观察到电压-心率反应曲线明显钝化,RSG功能显著降低,RSG神经活性频率和振幅明显减小,差异均有统计学意义(P<0.05)。且A-803467的浓度越高,电压-心率反应曲线钝化程度越大,RSG功能降低越显著,频率和振幅越小。结论阻断Nav1.8通道可以抑制RSG功能和神经活性,且阻断剂浓度越大,抑制效应越强。

Objective To investigate the effects of blocking Nav1.8 channels with its specific blocker A-803467 on the function and neural activity of the right stellate ganglia（RSG）. Methods Twenty-four pentobarbital anesthetized dogs were randomly divided into the control group and the low-concentration, medium-concentration, and high-concentration A-803467 groups, in which a volume of 0.1 m L of dimethylsulfoxide（DMSO）, low, medium, high concentrations of A-803467 were injected into the RSG, respectively. The maximum heart rate changes in response to RSG stimulation, and the changes in frequency and amplitude of neural activity of RSG were measured before and 30 min after the injection. The voltage-HR response curves were applied to represent the RSG function. Results At baseline,there were no significant differences among the four groups in the function and neural activity of RSG（P〈0.05）. At 30 min after injection, with the increase of the concentration of A-803467, voltage-HR response curves were significantly passivated, and RSG function, frequency and amplitude of neural activity of RSG were significantly decreased, in a concentration-dependent manner（P〈0.05）. Conclusion Blocking Nav1.8 channel can suppress the function and neural activity of RSG, in a concentration-dependent manner.