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Electrophysiological effects of AFD‐21 and AFD‐19, new antiarrythmic compounds on papillary muscles and single ventricular myocytes isolated from guinea‐pig hearts
Author(s) -
Kodama Itsuo,
Kamiya Kaichiro,
Kawamura Takashi,
Suzuki Ryoko,
Toyama Junji
Publication year - 1990
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.1476-5381.1990.tb14161.x
Subject(s) - electrophysiology , medicine , chemistry , membrane potential , guinea pig , sodium channel , resting potential , cardiology , sodium , biochemistry , organic chemistry
1 The effects of AFD‐21, a newly synthesized antiarrhythmic compound, and AFD‐19, its active metabolite, on transmembrane action potentials were examined in right ventricular papillary muscles and single ventricular myocytes isolated from guinea‐pig hearts. 2 In papillary muscles, AFD‐21 10 −5 m caused a slight prolongation of action potential duration (APD), while AFD‐19 above 10 −6 m shortened APD in a dose‐dependent manner. 3 Both AFD‐21 and AFD‐19 above 10 −6 m caused a significant and dose‐dependent decrease in the maximum upstroke velocity () of the action potential without affecting the resting membrane potential. 4 In the presence of AFD‐21 or AFD‐19, trains of stimuli at rates ≥ 0.2 Hz led to an exponential decline in . This use‐dependent block was enhanced at higher stimulation frequencies. A time constant for the recovery of from the use‐dependent block was 2.9 s for AFD‐21 and 3.6 s for AFD‐19. 5 The curves relating membrane potential and were shifted by AFD‐21 (10 −5 m ) or AFD‐19 (10 −5 m ) to the direction of more negative potentials by 5.3 mV and 5.1 mV respectively. 6 In single ventricular myocytes treated with AFD‐21 (10 −5 m ) or AFD‐19 (10 −5 m ), of test action potentials preceded by conditioning clamp pulses to 0 mV was decreased progressively as the clamp pulse duration was prolonged. 7 These findings suggest that both AFD‐21 and AFD‐19 have use‐ and voltage‐dependent inhibitory action on the sodium channel by binding to the channel during its inactivated state, and that the unbinding rate is comparable to that of Class I antiarrhythmic drugs with intermediate kinetics.