钩藤碱抑制麻醉大鼠颈动脉窦压力感受性反射的研究

目的 研究钩藤碱(Rhy)对颈动脉窦压力感受性反射(CSB)的作用并探讨其作用机制.方法 利用隔离灌流大鼠颈动脉窦技术,确定各项功能参数,如阈压(TP)、饱和压(SP)、平衡压(EP)、工作范围(OR)、最大斜率(PS)和平均动脉压反射性下降幅度(RD)等.Rhy(10、50、100 μmol/L)溶于K-H液后灌流窦区,以斜坡方式升降窦内压来观察Rhy对CSB的影响.分别预先灌流一氧化氮合酶抑制剂L-NAME,钾通道阻断剂四乙铵(TEA)和L-型钙通道开放剂Bay K8644后再给予Rhy,观察它们对Rhy作用的影响.结果 Rhy浓度依赖性地抑制了CSB, 使其各功能参数改变, TP和SP增大,PS和RD均减小.Rhy的抑制作用不能被L-NAME(300 μmol/L)和 TEA(1 mmol/L)预处理所取消,而可被Bay K8644 (500 nmol/L)明显减弱.结论 Rhy抑制了CSB,此作用可能是通过减弱压力感受器的牵张敏感性离子通道的钙内流来实现,而与NO和钾通道无关.     

Effects of ApC, a sea anemone toxin, on sodium currents of mammalian neurons

We have characterized the actions of ApC, a sea anemone polypeptide toxin isolated from Anthopleura elegantissima, on neuronal sodium currents (I(Na)) using current and voltage-clamp techniques. Neurons of the dorsal root ganglia of Wistar rats (P5-9) in primary culture were used for this study. These cells express tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) I(Na). In current-clamp experiments, application of ApC increased the average duration of the action potential. Under voltage-clamp conditions, the main effect of ApC was a concentration-dependent increase in the TTX-S I(Na) inactivation time course. No significant effects were observed on the activation time course or on the current peak-amplitude. ApC also produced a hyperpolarizing shift in the voltage at which 50% of the channels are inactivated and caused a significant decrease in the voltage dependence of Na+ channel inactivation. No effects were observed on TTX-R I(Na). Our results suggest that ApC slows the conformational changes required for fast inactivation of the mammalian Na+ channels in a form similar to other site-3 toxins, although with a greater potency than ATX-II, a highly homologous anemone toxin.