Lidocaine block of human heart sodium channels expressed in Xenopus oocytes

• Published in: Journal of molecular and cellular cardiology Vol. 24; no. 11; pp. 1231 - 1236
• Main Authors: Chahine, M., Chen, L.-Q., Barchi, R.L., Kallen, R.G., Horn, R.
• Format: Journal Article
• Language: English
• Published: Kent Elsevier Ltd 01.11.1992; Elsevier
• Subjects: Animals; Antiarythmic agents; Binding Sites; Biological and medical sciences; Cardiovascular system; Cloning, Molecular; Complementary DNA; Expression; Female; Human heart; Humans; Lidocaine; Lidocaine - metabolism; Lidocaine - pharmacology; Medical sciences; Myocardium - metabolism; Oocyte; Oocytes - drug effects; Oocytes - metabolism; Pharmacology. Drug treatments; Sodium channel; Sodium Channels - drug effects; Sodium Channels - genetics; Sodium Channels - metabolism; Xenopus laevis; Human heart; Sodium channel; Complementary DNA; Lidocaine; Expression; Oocyte; Heart; Human; Heterologous system; Xenopus laevis; Amphibia; Salientia; Ionic channel; Gene expression; In vitro; Dose activity relation; Vertebrata; Sodium; Mechanism of action; Antiarrhythmia agent
• ISSN: 0022-2828; 1095-8584
• 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 ≤−100 mV, the IC 50 was 226 μ m, 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 ( K I=11 μ m) and low affinity for the resting state ( K r=3.9 m m). The quaternary amine derivative of lidocaine, QX-314, had no effect on Na current at an extracellular concentration of 1 m m.