花生四烯酸乙醇胺对乳鼠心肌细胞外向钾通道电流的影响

Effects of anandamide on outward potassium channel currents in isolated cardiomyocytes of neonatal rat

目的研究内源性大麻样物质花生四烯酸乙醇胺(AEA)对乳鼠心肌细胞瞬时外向钾电流(Ito)及持续外向钾电流(Isus)的作用。方法体外培养乳鼠心室肌细胞,应用全细胞膜片钳方法检测不同浓度的AEA对Ito及Isus的作用。结果20nmol/LAEA即可显著抑制心肌细胞Ito及Isus的电流密度(分别为16.13±3.31pA/pFvs14.48±1.97pA/pF,及11.17±3.25pA/pFvs10.16±3.21pA/pF;P均<0.01)。逐步增加AEA的浓度至100,500nmol/L及1,5,10μmol/L仍然对Ito及Isus有抑制作用,但对Ito电流密度抑制最多的是5μmol/LAEA,而对Isus电流密度产生最大抑制作用的AEA浓度为1μmol/L。结论AEA对体外培养的乳鼠心肌细胞的Ito及Isus具有抑制作用,这一作用在一定的药物浓度范围内随剂量增加而增加。

Objective To observe the effects of endocannabinoid substance anandamide on outward potassium currents in isolated cardiomyocytes of neonatal rat. Methods Ventricular cardiomyocytes of neonatal rats were cultured. The whole-cell voltage clamp method was applied to detect transient outward potassium current （Ito） and sustained outward potassium current （ Isus） before and after different dosages of anandamide were added into the extracellular fluid. Results Anandamide inhibited the current density of Ito and Isus by each dosage from 20 nmol/L to 10μmol/L. The inhibition was dose-dependent in a certain range of concentrations. The maximal inhibition of Ito was induced by AEA at concentration of 5μmol/L （19.15 ±3.03 pA/pF vs 11.60 ±2.99 pA/pF,P 〈 0.01 ） , whereas that of Isus was induced by AEA at concentration of 1μmol/L （13.03 ±4.01 pA/pF vs 7.51 ±2.46 pA/pF,P 〈 0.01 ）. Conclusion AEA may inhibit the outward potassium currents of neonatal rat cardiomyocytes and the inhibitory effects of AEA is dose-related in a certain range of concentrations.