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Antiarrhythmic agents act differently on the activation phase of the ACh‐response in guinea‐pig atrial myocytes
Author(s) -
Inomata Norio,
Ohno Tomochika,
Ishihara Takafumi,
Akaike Norio
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13448.x
Subject(s) - guinea pig , atrial myocytes , acetylcholine , myocyte , pharmacology , chemistry , medicine
1 Anti‐acetylcholine effects of pilsicainide, flecainide, disopyramide and propafenone on the acetylcholine (ACh)‐induced K + current ( I K.ACh ) were examined in dissociated guinea‐pig atrial myocytes under whole‐cell voltage clamp by the use of the ‘concentration‐clamp’ technique. 2 The I K.ACh was activated with a latency of about 100 ms after 1 μ m ACh application and desensitized to a steady‐state level. The latent period and the time to peak response were shortened with increasing ACh concentration. 3 The values of half‐maximal inhibition (IC 50 ) on the peak and steady state responses were 25 and 25 μ m for pilsicainide, 1.7 and 2.0 μ m for disopyramide, 19 and 2.0 μ m for flecainide and 0.7 and 0.2 μ m for propafenone, respectively. 4 Pilsicainide and disopyramide increased the latent period and the time to peak of I K.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 I K.ACh in a voltage‐independent manner. 5 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.