摘要
目的研究花生四烯酸(arachidonic acid,AA)对家兔单个心室肌细胞L型钙通道的作用及其抗心律失常作用的机制。方法采用酶解法分离得到家兔单个心室肌细胞,全细胞膜片钳技术记录单个心室肌细胞L-型钙电流(L-type calcium current,ⅠCa-L),用累积给药的方法在灌流液中加入不同浓度的AA,观察给药前后L-型钙电流的变化,统计学方法采用单因素方差分析。结果不同浓度的AA均能明显抑制心室肌细胞ⅠCa-L。3μmol/L,10μmol/L,20μmol/L的AA使ⅠCa-L峰电流密度从(10.79±0.93)pA/pF分别减少到(8.99±0.43)pA/pF、(7.60±0.35)pA/pF和(5.60±0.30)pA/pF(n=7,P〈0.05),经冲洗后ⅠCa-L可部分恢复,并且AA可使ⅠCa-L的Ⅰ-Ⅴ关系曲线上移,其形状和峰值电压保持不变;20μmol/L的AA使ⅠCa-L失活曲线左移,失活后恢复时间明显延长,但对激活曲线无明显影响。结论花生四烯酸可通过加快L-型钙通道失活,延长其失活后的恢复过程而减少细胞外钙离子的内流,延长有效不应期,从而发挥抗心律失常作用。
Objective To study the influence of arachidonic acid (AA) on L-type calcium channel in rabbits single cardiomyocyte and its mechanism of antiarrhythmia. Method The single ventricular cardiomyocyte was isolated by using enzyme dispersion method and whole-cell clamp-patch technique was used to record L-type calcium current. All data were analyzed using ANOVA. Results AA inhibited ⅠCa-L in a concentration-dependent manner. The application of 3 μmol/L, 10 μmol/L and 20 μmol/L arachidonic acid reduced the density of peak ⅠCa-L froro ( 10.79 ± 0. 93 ) pA/pF to ( 8.99 ±0.43 ) pA/pF to (7.60±0.35) pA/pF and to (5.60 ±0.30 ) pA/pF, respetively ( n = 7, P 〈 0. 01 ). The/Ca-L partially resumed after washout. The AA up-shifted the Ⅰ-Ⅴ curves of ⅠCa-L without changes of their shape, peak and reverse potentials. The AA also markedly shifted the inactivation curve to left, and prolonged the recorvery time from inactivation, but did not change the curve of calcium channel activation. Conclustions By acceleration of L-type calcium channel inactivation and prolongation of recorvery time from inactivation, arachidonic acid can reduce the calcium ion influe and prolong effective refractory period, playing the role of antiarrhythmia.
出处
《中华急诊医学杂志》
CAS
CSCD
北大核心
2009年第2期180-184,共5页
Chinese Journal of Emergency Medicine
基金
国家自然科学基金资助项目(No.30570727)
关键词
花生四烯酸
心室肌细胞
心律失常
L-型钙通道
膜片钳
Arachidonic acid
Ventricular myocytes
Arrhythmia
L-type calcium channel
Patch clamp