Antiarrhythmic agents act differently on the activation phase of the ACh‐response in guinea‐pig atrial myocytes

Abstract

Anti‐acetylcholine effects of pilsicainide, flecainide, disopyramide and propafenone on the acetylcholine (ACh)‐induced K+ current (IK.ACh) were examined in dissociated guinea‐pig atrial myocytes under whole‐cell voltage clamp by the use of the ‘concentration‐clamp’ technique. The IK.ACh was activated with a latency of about 100 ms after 1 μm ACh application and desensitized to a steady‐state level. The latent period and the time to peak response were shortened with increasing ACh concentration. The values of half‐maximal inhibition (IC50) on the peak and steady state responses were 25 and 25 μm for pilsicainide, 1.7 and 2.0 μm for disopyramide, 19 and 2.0 μm for flecainide and 0.7 and 0.2 μm for propafenone, respectively. Pilsicainide and disopyramide increased the latent period and the time to peak of IK.ACh in a concentration‐dependent manner. Flecainide and propafenone did not change the latent period, but shortened the time to peak and hastened the decay of IK.ACh in a voltage‐independent manner. The results suggest that the mechanisms underlying the anti‐acetylcholine effect of antiarrhythmic drugs are different among these drugs: i.e., pilsicainide and disopyramide mainly block the muscarinic ACh receptors while flecainide and propafenone inhibit the K+ channel itself as open channel blockers. 1993 British Pharmacological Society