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Block of cardiac sodium channels by amiodarone studied by using of action potential in single ventricular myocytes
Author(s) -
Honjo Haruo,
Kodama Itsuo,
Kamiya Kaichiro,
Toyama Junji
Publication year - 1991
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.1476-5381.1991.tb12228.x
Subject(s) - sodium channel , voltage clamp , chemistry , depolarization , time constant , membrane potential , patch clamp , repolarization , amiodarone , hyperpolarization (physics) , electrophysiology , resting potential , sodium , antiarrhythmic agent , anesthesia , medicine , biophysics , biochemistry , stereochemistry , biology , organic chemistry , nuclear magnetic resonance spectroscopy , electrical engineering , atrial fibrillation , engineering , heart disease
1 Acute effects of amiodarone on cardiac sodium channels were investigated in ventricular myocytes isolated from guinea‐pig hearts, and compared with those of lignocaine. 2 Transmembrane potential was recorded and controlled by whole‐cell current‐clamp and voltage‐clamp respectively through suction pipette electrodes. The maximum upstroke velocity () of the action potential was used as a qualitative index of sodium channel availability. 3 In myocytes treated with amiodarone (1 μ m ) or lignocaine (40 μ m ), of reference action potential elicited at 0.03 Hz was decreased by 6 ∼ 11%, indicating minimal tonic block of sodium channels. 4 Application of a single conditioning depolarization to those myocytes resulted in a significant decrease in of a subsequent test action potential. The reduction was enhanced in a single exponential function as the clamp pulse duration was prolonged. Time constants at 0 mV clamp were 25 ms for amiodarone and 122 ms for lignocaine. 5 recovery of test action potential following a 1000 ms 0 mV clamp was approximated by a dual exponential function. Time constants for the late slow component (τ R ) at the resting potential level were 418 ms for amiodarone and 178 ms for lignocaine. τ R values were shortened in a voltage‐dependent manner by hyperpolarization during the coupling interval. 6 These findings suggested that amiodarone, like lignocaine, blocks the sodium channel primarily when it is in the inactivated state. Both onset and offset kinetics of the block are very rapid. Such sodium channel blocking characteristics may contribute to its potent antiarrhythmic activity.