Myocardial action potential and action of antiarrhythmic drugs
- Jonathan C Makielski, MD, FACC
Jonathan C Makielski, MD, FACC
- Professor of Medicine
- University of Wisconsin-Madison
Cardiac excitability refers to the ease with which cardiac cells undergo a series of events characterized by:
●Sequential depolarization and repolarization
●Communication with adjacent cells
●Propagation of the electrical activity in a normal or abnormal manner
The heartbeat arises from organized flow of ionic currents through ion-specific channels in the cell membrane, through the myoplasm and gap junctions that connect cells, and through the extracellular space (figure 1) [1,2]. Abnormal excitability leading to arrhythmia can arise from acquired or inherited abnormalities of these elements. Acquired abnormalities in cardiomyopathy are called electrical remodeling. Inherited abnormalities arise from mutations in genes encoding the subunits and associated proteins of these channels and have been associated with familial arrhythmic syndromes and sudden cardiac death. Examples include the congenital long QT syndrome (sodium and potassium current), the Brugada syndrome (mainly sodium current), and congenital heart block (sodium current). (See "Genetics of congenital and acquired long QT syndrome" and "Brugada syndrome: Epidemiology and pathogenesis" and "Etiology of atrioventricular block", section on 'Familial disease'.)
- Arnsdorf MF. The cellular basis of cardiac arrhythmias. A matrical perspective. Ann N Y Acad Sci 1990; 601:263.
- Fozzard HA, Arnsdor MF. Cardiac electrophysiology. In: The Heart and Cardiovascular System, Fozzard HA, Haber E, Jennings A, et al (Eds), Raven Press, New York 1991. p.63.
- Grant AO. Cardiac Ion Channels. Circ Arrythm Electrophysiol 2009; 2:185.
- Catterall WA. Structure and function of voltage-sensitive ion channels. Science 1988; 242:50.
- Stühmer W, Conti F, Suzuki H, et al. Structural parts involved in activation and inactivation of the sodium channel. Nature 1989; 339:597.
- Fozzard HA, Danck DA. Sodium channels. In: The Heart and Cardiovascular System, Fozzard HA, Haber E, Jennings A, et al (Eds), Raven Press, New York 1991. p.1091.
- The Sicilian gambit. A new approach to the classification of antiarrhythmic drugs based on their actions on arrhythmogenic mechanisms. Task Force of the Working Group on Arrhythmias of the European Society of Cardiology. Circulation 1991; 84:1831.
- Liu DW, Gintant GA, Antzelevitch C. Ionic bases for electrophysiological distinctions among epicardial, midmyocardial, and endocardial myocytes from the free wall of the canine left ventricle. Circ Res 1993; 72:671.
- Pelzer D, Pelzer S, McDonald TF. Calcium channels in heart. In: The Heart and Cardiovascular System,, Fozzard HA, Haber E, Jennings A, et al (Eds), Raven Press, New York1 991. p.1049.
- Snyders DJ, Hondeghem LM, Bennett PB. Mechanisms of drug-channel interaction. In: The Heart and Cardiovascular System, Fozzard HA, Haber E, Jennings A, et al (Eds), Raven Press, New York 1991. p.2165.
- Arnsdorf MF. Arnsdorf's paradox. J Cardiovasc Electrophysiol 1990; 1:42.
- Arnsdorf MF. Cardiac excitability, the electrophysiologic matrix and electrically induced ventricular arrhythmias: order and reproducibility in seeming electrophysiologic chaos. J Am Coll Cardiol 1991; 17:139.
- Hondeghem LM, Katzung BG. Antiarrhythmic agents: the modulated receptor mechanism of action of sodium and calcium channel-blocking drugs. Annu Rev Pharmacol Toxicol 1984; 24:387.
- Antzelevitch C, Nesterenko V, Shryock JC, et al. The role of late I Na in development of cardiac arrhythmias. Handb Exp Pharmacol 2014; 221:137.
- Podrid PJ, Fuchs T, Candinas R. Role of the sympathetic nervous system in the genesis of ventricular arrhythmia. Circulation 1990; 82:I103.
- Frishman W, Silverman R. Clinical pharmacology of the new beta-adrenergic blocking drugs. Part 2. Physiologic and metabolic effects. Am Heart J 1979; 97:797.
- Naccarelli GV, Lukas MA. Carvedilol's antiarrhythmic properties: therapeutic implications in patients with left ventricular dysfunction. Clin Cardiol 2005; 28:165.
- Hondeghem LM, Snyders DJ. Class III antiarrhythmic agents have a lot of potential but a long way to go. Reduced effectiveness and dangers of reverse use dependence. Circulation 1990; 81:686.