Abstract
1. The effects of the Class 1 antiarrhythmic agents lignocaine and quinidine on action potentials, and on sodium currents and potassium currents activated by depolarization, were examined in rat isolated ventricular myocytes by the whole cell, tight seal recording technique. 2. Tetrodotoxin and lignocaine shortened, whereas quinidine prolonged, the duration of the plateau phase of action potentials. 3. At low concentrations, lignocaine and quinidine blocked a persistent sodium current that was resistant to inactivation but they had only a small effect on the transient sodium current. At higher concentrations, they also blocked the transient sodium current. 4. Quinidine, but not tetrodotoxin or lignocaine, depressed potassium currents activated by depolarization and this could account for the prolongation of the plateau phase caused by quinidine. 5. It is suggested that block of the persistent sodium current may be responsible, at least in part, for the antiarrhythmic action of lignocaine and quinidine.
Full text
PDF





Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Abraham S., Beatch G. N., MacLeod B. A., Walker M. J. Antiarrhythmic properties of tetrodotoxin against occlusion-induced arrhythmias in the rat: a novel approach to the study of the antiarrhythmic effects of ventricular sodium channel blockade. J Pharmacol Exp Ther. 1989 Dec;251(3):1166–1173. [PubMed] [Google Scholar]
- Balser J. R., Bennett P. B., Hondeghem L. M., Roden D. M. Suppression of time-dependent outward current in guinea pig ventricular myocytes. Actions of quinidine and amiodarone. Circ Res. 1991 Aug;69(2):519–529. doi: 10.1161/01.res.69.2.519. [DOI] [PubMed] [Google Scholar]
- Clarkson C. W., Follmer C. H., Ten Eick R. E., Hondeghem L. M., Yeh J. Z. Evidence for two components of sodium channel block by lidocaine in isolated cardiac myocytes. Circ Res. 1988 Nov;63(5):869–878. doi: 10.1161/01.res.63.5.869. [DOI] [PubMed] [Google Scholar]
- Colatsky T. J. Mechanisms of action of lidocaine and quinidine on action potential duration in rabbit cardiac Purkinje fibers. An effect on steady state sodium currents? Circ Res. 1982 Jan;50(1):17–27. doi: 10.1161/01.res.50.1.17. [DOI] [PubMed] [Google Scholar]
- Coraboeuf E., Deroubaix E., Coulombe A. Effect of tetrodotoxin on action potentials of the conducting system in the dog heart. Am J Physiol. 1979 Apr;236(4):H561–H567. doi: 10.1152/ajpheart.1979.236.4.H561. [DOI] [PubMed] [Google Scholar]
- Farmer B. B., Mancina M., Williams E. S., Watanabe A. M. Isolation of calcium tolerant myocytes from adult rat hearts: review of the literature and description of a method. Life Sci. 1983 Jul 4;33(1):1–18. doi: 10.1016/0024-3205(83)90706-3. [DOI] [PubMed] [Google Scholar]
- Hamill O. P., Marty A., Neher E., Sakmann B., Sigworth F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. doi: 10.1007/BF00656997. [DOI] [PubMed] [Google Scholar]
- Hiraoka M., Sawada K., Kawano S. Effects of quinidine on plateau currents of guinea-pig ventricular myocytes. J Mol Cell Cardiol. 1986 Oct;18(10):1097–1106. doi: 10.1016/s0022-2828(86)80296-6. [DOI] [PubMed] [Google Scholar]
- Hoffman B. F., Rosen M. R., Wit A. L. Electrophysiology and pharmacology of cardiac arrhythmias. VII. Cardiac effects of quinidine and procaine amide. A. Am Heart J. 1975 Jun;89(6):804–808. doi: 10.1016/0002-8703(75)90197-0. [DOI] [PubMed] [Google Scholar]
- Imaizumi Y., Giles W. R. Quinidine-induced inhibition of transient outward current in cardiac muscle. Am J Physiol. 1987 Sep;253(3 Pt 2):H704–H708. doi: 10.1152/ajpheart.1987.253.3.H704. [DOI] [PubMed] [Google Scholar]
- Makielski J. C., Alpert L. A., Hanck D. A. Two components of use-dependent block of sodium current by lidocaine in voltage clamped cardiac Purkinje cells. J Mol Cell Cardiol. 1991 Feb;23 (Suppl 1):95–102. doi: 10.1016/0022-2828(91)90028-k. [DOI] [PubMed] [Google Scholar]
- Nilius B. Modal gating behavior of cardiac sodium channels in cell-free membrane patches. Biophys J. 1988 Jun;53(6):857–862. doi: 10.1016/S0006-3495(88)83166-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rosen M. R., Hoffman B. F., Wit A. L. Electrophysiology and pharmacology of cardiac arrhythmias. V. Cardiac antiarrhythmic effects of lidocaine. Am Heart J. 1975 Apr;89(4):526–536. doi: 10.1016/0002-8703(75)90162-3. [DOI] [PubMed] [Google Scholar]
- Saint D. A., Ju Y. K., Gage P. W. A persistent sodium current in rat ventricular myocytes. J Physiol. 1992;453:219–231. doi: 10.1113/jphysiol.1992.sp019225. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Starmer C. F., Nesterenko V. V., Undrovinas A. I., Grant A. O., Rosenshtraukh L. V. Lidocaine blockade of continuously and transiently accessible sites in cardiac sodium channels. J Mol Cell Cardiol. 1991 Feb;23 (Suppl 1):73–83. doi: 10.1016/0022-2828(91)90026-i. [DOI] [PubMed] [Google Scholar]
- Zhou J. Y., Potts J. F., Trimmer J. S., Agnew W. S., Sigworth F. J. Multiple gating modes and the effect of modulating factors on the microI sodium channel. Neuron. 1991 Nov;7(5):775–785. doi: 10.1016/0896-6273(91)90280-d. [DOI] [PubMed] [Google Scholar]