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.
Maier
Sebastian K G
SK
Medizinische Universitätsklinik Würzburg, Germany. smaier@medizin.uni-wuerzburg.de
Kirstein
Michael
M
D000200:Action Potentials / Q000187:drug effects; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001262:Atenolol / Q000494:pharmacology; D022062:Electrophysiologic Techniques, Cardiac; D005260:Female; D006352:Heart Ventricles; D007545:Isoproterenol / Q000494:pharmacology; D023421:Models, Animal; D008955:Models, Cardiovascular; D009206:Myocardium / Q000737:chemistry* / Q000378:metabolism*; D011405:Propafenone / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000187:drug effects*; D013268:Stimulation, Chemical
D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D015222:Sodium Channels; D001262:Atenolol; D011405:Propafenone; D007545:Isoproterenol