Inhibition by local anesthetics of Ca2+ channels in rat anterior pituitary cells.
Inhibition by local anesthetics of Ca2+ channels in rat anterior pituitary cells.
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DOI：
10.1016/s0014-2999(98)00769-9
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发表时间：
1998-12
影响因子：
5
通讯作者：
Zhiling Xiong;Zhiling Xiong;Gary R. Strichartz;Gary R. Strichartz
中科院分区：
文献类型：
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作者：
Zhiling Xiong;Zhiling Xiong;Gary R. Strichartz;Gary R. Strichartz
用全细胞电压钳技术研究了局麻药对大鼠垂体细胞系电压依赖性钙通道的抑制特性，并与二氢吡啶类钙通道拮抗剂尼卡地平的抑制作用进行了比较。以细胞外Ba 2+（10 mM）作为电流载体，高于-40 mV的去极化引起缓慢失活的IBa。细胞外应用利多卡因抑制IBA，但不改变激活阈值、峰电流电压和反转电位。在保持电位为−60 mV（IC 50 =1.2 mM）时的抑制作用大于在−80 mV（IC 50 =2.6 mM）时的抑制作用。这种去极化诱导的增强作用在IBain中在膜去极化开始后的0.1-10秒内发展。尼卡地平也剂量依赖性地抑制IBA，IC 50 =90 nM（保持电位=−80 mV）。利多卡因和尼卡地平均使IBasteady状态失活（可用性）曲线左移。双脉冲方案显示，利多卡因（1 mM）加速去极化诱导的抑制（失活）的IBaover的速率在无药物的解决方案，但没有影响超极化诱导的通道失活的去除。尼卡地平还加速了IBabut的去极化失活，并减慢了超极化失活的清除。尼卡地平存在时，利多卡因抑制IBa的相对抑制作用不变。这些结果表明，利多卡因对膜Ca 2+通道具有直接作用，类似于二氢吡啶的电压依赖性作用，但作用于单独且独立的位点。
The characteristics of local anesthetic inhibition of voltage-dependent Ca2+channels in a rat pituitary clonal cell line were investigated by whole-cell voltage clamp and compared with inhibition by the dihydropyridine Ca2+channel antagonist, nicardipine. With extracellular Ba2+(10 mM) as the current carrier, depolarization above −40 mV evoked a slowly inactivating IBa. Extracellularly applied lidocaine inhibited IBawithout changing the activation threshold, the voltage of peak current, or the reversal potential. Inhibition was greater at a holding potential of −60 mV (IC50=1.2 mM) than at −80 mV (IC50=2.6 mM). This depolarization-induced potentiation in IBainhibition developed over 0.1–10 s after membrane depolarization began. Nicardipine also dose-dependently inhibited IBawith an IC50=90 nM (at a holding potential=−80 mV). Both lidocaine and nicardipine shifted the IBasteady-state inactivation (availability) curves to the left. Double-pulse protocols revealed that lidocaine (1 mM) accelerated the depolarization-induced inhibition (inactivation) of IBaover the rate in drug-free solutions, but had no effect on the hyperpolarization-induced removal of channel inactivation. Nicardipine also accelerated the depolarization-induced inactivation of IBabut, in addition, it slowed the hyperpolarization-induced inactivation removal. The relative inhibitory action of lidocaine in suppressing IBawas unchanged in the presence of nicardipine. These results suggest that lidocaine has a direct action on membrane Ca2+channels, similar to the voltage-dependent action of dihydropyridine, but acting at a separate and independent site.