Toth P T, Vizi E S
Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Hungary.
Eur J Pharmacol. 1998 Dec 11;363(1):75-80. doi: 10.1016/s0014-2999(98)00743-2.
The effect of lobeline was studied on the voltage-activated Ca2+ current in sympathetic neurones from the rat superior cervical ganglia using the whole-cell variant of the patch-clamp technique. Lobeline (10-300 microM) inhibited the Ca2+ current evoked by voltage steps from -80 mV (holding potential) to 0 mV (test potential) in a dose dependent manner. The inhibitory effects of noradrenaline (10 microM) and lobeline (100 microM) were compared using a prepulse protocol with high (+80 mV) depolarization. Within the same cell depolarizing prepulses decreased the inhibitory effect of noradrenaline but did not change the extent of lobeline inhibition. Addition of GTPgammaS (300 microM) to the pipette solution did not prevent the inhibitory effect of lobeline (100 microM) but greatly reduced that of noradrenaline (100 microM). Our experiments suggest, that the weak nicotinic agonist lobeline exerts a direct blocking effect on Ca2+ channels at concentrations commonly used to release transmitters.
运用膜片钳技术的全细胞变体，研究了洛贝林对大鼠颈上神经节交感神经元电压激活的Ca2+电流的影响。洛贝林（10 - 300微摩尔）以剂量依赖方式抑制了从-80毫伏（钳制电位）到0毫伏（测试电位）的电压阶跃诱发的Ca2+电流。使用具有高（+80毫伏）去极化的预脉冲方案比较了去甲肾上腺素（10微摩尔）和洛贝林（100微摩尔）的抑制作用。在同一细胞内，去极化预脉冲降低了去甲肾上腺素的抑制作用，但未改变洛贝林的抑制程度。向移液管溶液中添加GTPγS（300微摩尔）并不能阻止洛贝林（100微摩尔）的抑制作用，但大大降低了去甲肾上腺素（100微摩尔）的抑制作用。我们的实验表明，弱烟碱激动剂洛贝林在常用于释放递质的浓度下对Ca2+通道发挥直接阻断作用。
