Effects of mibefradil, a T-type calcium current antagonist, on electrophysiology of Purkinje fibers that survived in the infarcted canine heart.
Effects of mibefradil, a T-type calcium current antagonist, on electrophysiology of Purkinje fibers that survived in the infarcted canine heart.
复制标题
米贝拉地尔（一种 T 型钙电流拮抗剂）对梗塞犬心脏中存活的浦肯野纤维电生理学的影响。
DOI：
10.1111/j.1540-8167.1999.tb00300.x
复制
发表时间：
1999
影响因子：
2.7
通讯作者：
Boyden,PA
中科院分区：
文献类型：
--
作者：
Pinto,JM;Sosunov,EA;Gainullin,RZ;Rosen,MR;Boyden,PA
米贝弗拉迪对犬浦肯野肌细胞的影响。简介：我们研究了非二氢吡啶T型Ca2+通道拮抗剂米贝弗拉迪（MIB）对正常（NZPC）和48小时梗死（IZPC）心脏左心室心内膜下分散的浦肯野肌细胞中T型和L型Ca2+(ICaT, ICaL)电流的影响。方法和结果：用富含Cs*‐和EGTA的移液器和不含Na+‐K+‐的外部溶液记录电流，以消除重叠电流。在所有细胞中，ica1均被0.1 ~ 10 μM的MIB降低。观察到ica峰衰减的时间过程没有变化。当MIB浓度为1 μM时，NZPCs的平均峰值T/L比降低，而IZPCs则没有。在两种细胞类型（平均±SEM）中，I μM MIB改变了icall的稳态可用性（给药前，NZPC的V0.5=‐22±4 mV， IZPC的V0.5=‐25±5 mV；给药后，NZPC的V0.5=‐63±9 mV， IZPC的V0.5=‐67±6 mV, P < 0.05）。ICaTV0.5（给药前NZPC为‐50±3 mV， IZPC为‐52±1 mV）在给药后（NZPC为‐60±2 mV）和（IZPC为‐62±3 mV）变化（P < 0.05）。我们还使用标准微电极技术确定了MIB对自发加热浦肯野正常纤维和梗死心脏异常自动纤维去极化的影响。当[K+]0= 2.7 mM时，MIB 3 μM和10 μM对速率和最大舒张电位没有影响，但动作电位平台向负值偏移，复极化第3相斜率减小，动作电位持续时间增加。结论：MIB阻断浦肯野肌细胞中的L型和T型Ca2+电流，但对浦肯野纤维的正常或异常自动性缺乏影响。
Mibefradil's Effects on Canine Purkinje Myocytes.Introduction: We studied the effects of mibefradil (MIB), a nondihydropyridine T‐type Ca2+channel antagonist, on T‐ and L‐type Ca2+(ICaT, ICaL) currents in Purkinje myocytes dispersed from the subendocardium of the left ventricle of normal (NZPC) and 48‐hour infarcted (IZPC) hearts.Methods and Results: Currents were recorded with Cs*‐ and EGTA‐rich pipettes and in Na+‐K+‐free external solutions to eliminate overlapping currents. In all cells, ICawas reduced by MIB (0.1 to 10 μM). No change in the time course of decay of peak ICawas noted. Average peak T/L ratio decreased in NZPCs hut not IZPCs with 1 μM MIB. Steady‐state availability of ICaLwas altered with I μM MIB in both cell types (mean ± SEM) (V0.5= ‐22 ± 4 mV for NZPC and ‐25 ± 5 mV for IZPC before drug; ‐63 ± 9 mV for NZPC and ‐67 ± 6 mV for IZPC after drug: P < 0.05). For ICaTV0.5(‐50 ± 3 mV for NZPC and ‐52 ± 1 mV for IZPC before drug) shifted 10 ‐60 ± 2 mV (NZPC) and ‐62 ± 3 mV (IZPC) (P < 0.05) after drug. We also determined the effects of MIB on spontaneously heating Purkinje normal fibers and on depolarized abnormally automatic fibers from the infarcted heart using standard microelectrode techniques. When NZPC and IZPC fibers were superfused with [K+]0= 2.7 mM, MIB 3 μM and 10 μM had no effect on rate or the maximum diastolic potential, but action potential plateau shifted to more negative values, the slope of repolarization phase 3 decreased, and action potential duration increased.Conclusion: MIB blocks L‐ and T‐type Ca2+currents in Purkinje myocytes hut lacks an effect on either normal or abnormal automaticity in Purkinje fibers.