Effects of Berberine Derivate CPU 86017 on IKur Currents and Experimental Atrial Fibrillation

AimCompared with azimilide, the present study was designed to observe the anti-atrial fibrillation (AF) effects of CPU 86017, a berberine derivative, and explore its possible ion-channel mechanism.MethodsThe effects of CPU 86017 on ultra-rapid delayed rectifier K+ current (IKur) was studied both on guinea pigs atrial cardiomyocytes and human embryonic kidney (HEK) 293 cell line with whole-cell patch clamp technique. Anti-AF action of CPU 86017 (1.25, 2.5 mg·kg−1, ip) was observed in AF model rats induced by acetylcholine (ACh)-CaCl2.ResultsCPU 86017 inhibited IKur in a concentration-dependent manner. The IC50 of IKur on atrial myocytes and HEK293 cells was 4.56 and 0.21 μmol·L−1, respectively. On the AF rats, CPU 86017 effectively shortened AF duration, prolonging atrial effective refractory period (AERP) by 38.9% in rats atrial.ConclusionCPU86017 inhibited IKur in a concentration-dependent manner. It was effective in treating AF partly by inhibiting IKur and prolonging AERP.

摘 要目的：研究小檗碱衍生物CPU 86017对抗房颤作用及其离子通道机制。方法：运用膜片钳技术在稳定表达人心房肌Kv1.5钾通道细胞系(HEK293)及豚鼠心房肌细胞上观察CPU 86017对超速整流钾通道(IKur)的作用, 观察CPU 86017 (1.25或2.5 mg·kg−1)对比阳性药azimilide (3 mg·kg−1)对乙酰胆碱(ACh)和CaCl2诱发的大鼠房颤的治疗作用。结果：CPU 86017依浓度抑制IKur, 对豚鼠心房肌细胞和培养的HEK293细胞上IKur的半数抑制浓度(IC50)分别是4.56和0.21 μmol·L−1。在乙酰胆碱(ACh)和CaCl2诱发的房颤模型上, CPU 86017有效缩短房颤持续时间, 逆转房颤所致心房有效不应期(AERP)的缩短。结论：CPU 86017能抑制KV1. 5编码的电流IKur, 改善房颤大鼠心房ERP的病变, 有效对抗房颤。