AIM: To study the effects of berberine on inward rectifier potassium current (Ik1) and outward delayed rectifier potassium current (Ik) of guinea pig ventricular my ocytes, and on human ether-a-go-go related gent (HERG) channel expressed in Xenopus oocytes. METHODS: Whole cell patch-clamp and geneclamp techniques were used to record ionic currents.RESUTS: Berberine prolonged action potential duration (APD) and inhibited Ik1 and Ik in a concentration-dependent manner. Berberine 100μmo1/L increased APD90 from (450±48) ms to (888±90) ms (n=6,P<0.01), and inhibited Ik1 by 64%±7%(n=6,P<0.01). Berberine 50μmo1/L inhibited Ik by 57%±6%,Iktmil by 52%±6%(n=6,P<0.01). Berberine produced a voltage-dependent block on Ik that increased with stronger depolarization, and once all channels activated, there was no further block at positive potentials. Berberine blocked the HERG channels potently with an IC50 value of approximately 75μmo1/L. This block was voltage-dependent, suggesting that it probably bind to either open or inactivated HERG channels. CONCLUSION: Berberine prolonged APD and possessed blocking effect on Ik1,Ik, and HERG channel expressed in Xenopus oocytes. The antiarrhythmic mechanism of berberine is related to its inhibitory effects on Ik1,Ik,and HERG channel.

采用全细胞电压钳技术, 以确定青蒿素对分离的豚鼠心室肌细胞和狗的浦肯野纤维钾离子电流的影响. 在豚鼠心室肌细胞, 青蒿素呈浓度依赖关系显著降低内向整流钾电流(IK1, 膜电位为- 100mV 时, IC50为(7. 2±0. 8) Lmol·L-1), 且这种抑制作用不呈现频率依赖性. 50 Lmol·L21的青蒿素降低延迟整流钾电流(I K) : 时间依赖性外向钾电流(IKstep) 在膜电位为+ 40 mV 时减少(38±10)%. 尾电流步阶分析提示, IK 的快组分(IKr) 和慢组分(I Ks)均被抑制. 在犬浦肯野纤维, 青蒿素明显抑制瞬时外向钾电流(Ito), IC50为(4. 2±0. 3) Lmol·L-1. 实验结果表明, 青蒿素以相似效率抑制I K1, I to 和I K,其抗心律失常作用可能与抑制I K1, I to, I Kr和I Ks有关。

The effects of artemisin in on the potassium ionic currents of guinea pig ventricular cells and dog Purkinje fibres were studied using the whole cell voltage clamp technique. Artemisin in significantly decreased inward rectifier K+ current (IK1) with an IC50 of (7. 2

n injury by the generation of peroxynitrite. Although polyamines have been implicated in tissue ischemia injury, their metabolism and interactions with NO in myocardial ischemia/reperfusion injury have not been fully understood. In our experiment, when Langendorff perfused rat hearts were subjected to 40 min ischemia without reperfusion, both ornithine decarboxylase (ODC) and Spermidine/spermine N1-acetyltransferase (SSAT) activities were up-regulated and putrescine accumulated. While after reperfusion, ODC activity decreased and SSAT activity increased, resulting in putrescine accumulation and decreased spermidine and spermine. Meanwhile NO content was increased. In addition, sodium nitroprusside (SNP, a NOdonor) decreased ODC activity in cardiac tissue homogenate but increased SSAT activity in a dose-dependent manner. Pre-treatment of isolated heart with Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME, an inhibitor of NO synthase) increased ODC activity. Exogenous spermine (1 mM) administration prior to ischemia prevented spermine decrease, reduced cardiac myocyte necrosis and apoptosis, and promoted the recovery of cardiac function after ischemia/reperfusion. These results suggest that acute heart ischemia activates myocardial polyamine stress response characterized by increased ODC and SSAT activities and accumulation of putrescine. Ischemia/reperfusion disturbs polyamine metabolism, and the loss of spermine might be associated with NO increase and thereby influences myocardial cell viability. Exogenous spermine may protect the hearts from myocardial ischemia/reperfusion injury.