【摘要】 目的　研究氯苄基四氢小檗碱 (CPU) 86 0 35对豚鼠单个心室肌细胞L型钙通道的抑制作用 ,分析对L型钙通道相互作用的状态依赖性。方法　采用膜片钳全细胞技术 ,记录不同浓度(5 0～ 2 5 0 μmol/L)CPU86 0 35作用前后的L型钙电流 (ICa L)。结果　 (1)CPU86 0 35呈剂量依赖性地抑制L型钙电流 ,半数抑制浓度 (IC50 )为 75 μmol/L。(2 )CPU86 0 35对L型钙电流的抑制依赖于保持电位(HP)。HP =- 4 0mV时 ,75 μmol/LCPU86 0 35的抑制率为 4 9%± 2 % ,HP =- 80mv时 ,抑制率为6 4 %± 4 %。 (3)CPU86 0 35作用后 ,稳态激活曲线右移 ,V1/ 2 由对照的 6 7mV± 1 6mV变为 15 4mV±0 8mV。 (4)CPU 86 0 35作用后 ,稳态失活曲线右移 ,V1/ 2 由对照的 - 19 1mV± 2 5mV变为 - 12 6mV± 2 7mV。 (5 )用药后L型钙通道从失活状态恢复的时间变长。结论　CPU86 0 35对L型钙通道有较强的抑制作用 ,药物可能主要与通道的静息状态结合更多还原

【Abstract】 Objective To investigate the effects of CPU86035, a recently synthesized tetrahydroberberine derivative, on the L type calcium currents (I Ca L ) in single guinea pig ventricular myocytes Methods The effect of CPU86035 of different concentrations (50～250 μmol/L) on I Ca L in enzymatically dispersed single guinea pig ventricular myocytes was investigated by using whole cell patch clamp technique Results (1) CPU86035 concentration dependently inhibited I Ca L , with the IC50 at 75 μmol/L (2) The inhibition of CPU86035 on I Ca L was dependent on the holding potential (HP) 75 μmol/L CPU86035 inhibited I Ca L by 49%±2% at HP=-40 mV, and 64%±4% at HP=-80 mV (3) The homeostatic activation curve of ICa L shifted to the right toward more positive potentials in the presence of CPU86035, with a V 1/2 of 15 4 mV±0 8 mV compared with that of 15 4±0 8 mV in the control (4) The homeostatic inactivation curve of I Ca L shifted to the right toward more positive potentials in the presence of CPU86035, with a V 1/2 of -12 6 mV±2 7 mV compared with that of -19 1 mV± 2 5 mV in the control (5) The recovery from inactivation became slower in the presence of CPU86035 Conclusion CPU86035 strongly inhibits the calcium channel, probably by binding to the channel in resting stage更多还原