Beta-adrenergic stimulation modulates the sodium current block by propafenone in rat ventricular myocardium

Propafenone is a class I antiarrhythmic drug used to suppress cardiac arrhythmia both of atrial and ventricular origin. We measured fast sodium current (I(Na)+) directly with the loose-patch-clamp technique and confirm the frequency-dependent block of this current. Effects on steady-state current kinetics were small or even in the opposite direction. Since propafenone interacts with the beta-adrenergic receptor and stimulation of this receptor itself increases I(Na)+, propafenone was combined with isoproterenol (100 nmol/L). Now we found an augmentation of the frequency-dependent block of I(Na)+. Together with the beta-receptor antagonist atenolol, propafenone exhibited more class I potency but the frequency-dependent block of propafenone was only slightly increased. We conclude that the augmentation of the frequency-dependent effect was predominantly due to phosphorylation of the sodium channel and not due to displacement of propafenone from the beta-receptor. Nevertheless, in clinical settings with various states of the sympathetic tone one has to be aware of different propafenone effects.