Chahine M, Chen L Q, Barchi R L, Kallen R G, Horn R
Department of Neurosciences, Roche Institute of Molecular Biology, Nutley, NJ 07110.
J Mol Cell Cardiol. 1992 Nov;24(11):1231-6. doi: 10.1016/0022-2828(92)93090-7.
The tertiary amine lidocaine is used clinically for preventing cardiac arrhythmias, and has been widely studied on mammalian tissue. Xenopus oocytes were used as an expression system to study the effect of lidocaine on a sodium (Na) channel, derived from a full-length human heart (hH1) cDNA clone. The concentration dependence of the lidocaine block of hH1 Na current was consistent with a binding stoichiometry of 1:1. At low frequency stimulation, and at holding potentials < or = 100 mV, the IC50 was 226 microM, comparable to values found in mammalian cardiac cells. Lidocaine also shifted the steady-state inactivation of hH1 Na current to hyperpolarized potentials in a dose-dependent manner. Our experiments suggest that lidocaine block is state dependent, with high affinity for an inactivated state (KI = 11 microM) and low affinity for the resting state (KR = 3.9 mM). The quaternary amine derivative of lidocaine, QX-314, had no effect on Na current at an extracellular concentration of 1 mM.
叔胺利多卡因临床上用于预防心律失常，并且已在哺乳动物组织上进行了广泛研究。非洲爪蟾卵母细胞被用作表达系统，以研究利多卡因对源自全长人类心脏（hH1）cDNA克隆的钠（Na）通道的影响。利多卡因对hH1钠电流的阻断作用的浓度依赖性与1:1的结合化学计量比一致。在低频刺激下，以及在保持电位≤100 mV时，半数抑制浓度（IC50）为226 μM，与在哺乳动物心肌细胞中发现的值相当。利多卡因还以剂量依赖性方式将hH1钠电流的稳态失活转移到超极化电位。我们的实验表明，利多卡因阻断具有状态依赖性，对失活状态具有高亲和力（解离常数KI = 11 μM），对静息状态具有低亲和力（解离常数KR = 3.9 mM）。利多卡因的季胺衍生物QX-314在细胞外浓度为1 mM时对钠电流没有影响。
