Frequency-dependent blockade of T-type Ca2+ current by efonidipine in cardiomyocytes.
Frequency-dependent blockade of T-type Ca2+ current by efonidipine in cardiomyocytes.
复制标题
依福地平对心肌细胞中 T 型 Ca2 电流的频率依赖性阻断。
DOI：
10.1016/s0024-3205(00)00932-2
复制
发表时间：
2000
期刊：
影响因子：
6.1
通讯作者：
K. Shigenobu
中科院分区：
文献类型：
--
作者：
H. Masumiya;J. Kase;Y. Tanaka;H. Tanaka;K. Shigenobu
埃福尼地平是一种二氢吡啶类Ca2+拮抗剂，对l型和t型Ca2+通道均有抑制作用，对高心率患者具有明显的心脏活动迟缓作用。在本研究中，我们检测了依福尼地平对离体豚鼠心室肌细胞t型Ca2+通道的频率依赖性。在较高的刺激频率下，efonidipine抑制t型Ca2+电流的效价更高。刺激频率为1、0.2和0.05 Hz时，ic50值分别为1.3×10−8、2.0×10−6和6.3×10−6M。t型Ca2+电流幅值的降低不伴有电流衰减时间过程的变化。埃福尼地平（10 μM）对−90 ~−30 mV保持电位下脱极化引发的t型Ca2+电流抑制约30%；稳态失活的电压依赖性不受药物的影响。依福地平减缓了失活预脉冲后失活的恢复。总之，efonidipine被证明对t型Ca2+通道具有频率依赖性的抑制作用，这可以解释为药物从通道的失活状态缓慢解离。
Efonidipine is a dihydropyridine Ca2+ antagonist with inhibitory effects on both L-type and T-type Ca2+ channels and potent bradycardiac activity especially in patients with high heart rate. In the present study, we examined the frequency dependence of efonidipine action on the T-type Ca2+ channel in isolated guinea-pig ventricular myocytes. The potency of efonidipine to inhibit the T-type Ca2+ current was higher under higher stimulation frequencies. The IC50values were 1.3×10−8, 2.0×10−6and 6.3×10−6M under stimulation frequencies of 1, 0.2 and 0.05 Hz, respectively. The reduction of T-type Ca2+ current amplitude was not accompanied by change in the time course of current decay. Efonidipine (10 μM) inhibited T-type Ca2+ current elicited by depolarization from holding potentials ranging from −90 to −30 mV by about 30%; the voltage-dependence of steady-state inactivation was not changed by the drug. Efonidipine slowed the recovery from inactivation following an inactivating prepulse. In conclusion, efonidipine was shown to have frequency-dependent inhibitory effects on the T-type Ca2+ channel, which could be explained by slow dissociation of the drug from the inactivated state of the channel.