Basic Electrophysiological Actions of Propafenone in Heart Muscle

Abstract

The excitability of atrial and ventricular myocardium under physiological conditions depends on the ability of the cardiac membrane to respond to suprathreshold stimuli with an increase in Na⁺ permeability. This allows the occurrence of a fast Na⁺ inward current. However, action potential generation is not exclusively related to the availability of the fast Na⁺ system since Na⁺ inactivation as it develops after decreasing the resting potential to about −50 mV (Weidmann 1955 a) does not abolish excitability (Engstfeld et al. 1961). In this particular situation, slow response action potentials can be generated (Mascher 1970) mediated by another inward conductance system, the slow channel. This maintains excitability but may also be involved in the development of certain cardiac arrythmias (for review see Kohlhardt 1980). The antiarrhythmic effect of a drug, therefore, does not arise only from its affinity for fast Na⁺ channels — a fact which caused Vaughan Williams (1975) to introduce the classification of antiarrhythmics into four groups depending on the electrophysiological action. Class 1 compounds depress the fast Na⁺ current (I_Na) and comprise different drugs such as local anesthetics, quinidine, or certain β -receptor blockers with side effects on excitable membranes. Propafenone represents another member of class 1 though it loses the virtual specifity for the Na⁺ system when higher drug concentrations are applied. The latter phenomenon represents a widespread property of class 1 antiarrhythmics and is not peculiar to propafenone.