Influences of angiotensin II on calcium channel current and intracellular free calcium concentration of human atrial myocytes and the antagonistic effect of amiodarone

Objective To observe the influences of angiotensin Ⅱ (AngⅡ) on calcium channel current and intracellular free calcium concentration ([Ca 2+]i) of human atrial myocytes, so as to reveal the electrophysiological mechanisms of atrial arrhythmia induced by AngⅡ, and to investigate the antagonistic effect of amiodarone for providing the theoretical basis in treating atrial arrhythmias.Methods Single human atrial myocyte was isolated. The conventional whole-cell configuration of the patch-clamp technique was used to detect membrane I Ca-L, and confocal microscope was used with Fluo-3/AM as indicator to detect changes of [Ca 2+]i. The experiment comprised of four groups, ie, control group, AngⅡ group, amiodarone group and AngⅡ+amiodarone group.Results Comparing with the control group, AngⅡ of 0.1 μmol/L significantly increased the peak density of I Ca-L in human atrial myocyte [(-12.77±1.61) pA/pF vs (-5.78±0.81) pA/pF, P0.05). Amiodarone of 30 nmol/L had no significant effect on I Ca-L of human atrial myocyte [(-5.58±0.76) pA/pF], but it could antagonize the effects of AngⅡ. In AngⅡ+amiodarone group, the peak density of I Ca-L was [(-7.15±0.82)] pA/pF, which had a significant difference in comparing with the AngⅡ group (P0.05). The intracellular fluoresence intensity of single cardiomyocyte in both control and amiodarone groups was low. The intracellular fluoresence intensity of single cardiomyocyte in AngⅡ group was significantly higher than that in the control group after 15 minutes intervention (P0.05). When amiodarone was added simultaneously with AngⅡ intervention, the values were much lower comparing with AngⅡ group (P0.05).Conclusion AngⅡ of 0.1 μmol/L can significantly increase the peak density of I Ca-L and induce intracellular calcium overload in human atrial myocytes, which may participate in human atrial electrical remodeling and relevant to occurrence and progression of atrial fibrillation. Amiodarone can antagonize the above effects of AngⅡ in human atrial myocytes.