四氢小檗碱衍生物86035对豚鼠心室肌L型钙通道的抑制作用

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

Inhibitory action of CPU86035 on L-type calcium current in single ventricular myocyte of guinea pig

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 approximately 250 micromomol/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 micromol/L. (2) The inhibition of CPU86035 on I(Ca.L) was dependent on the holding potential (HP). 75 micromol/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.