Characterization of cardiac dysrhythmias induced by the modification of sodium channels and the inhibition of Na+-K+ Atpase in guinea pigs

Delayed afterdepolarizations (DADs) and triggered activity are the mechanisms by which lethal ventricular dysrhythmias are induced. A plenty of studies have been done with whole animal model, isolated heart and isolated cardiac muscles, however, there is no report on the abnormal automaticity in isolated cardiac myocytes. We induced, recorded and analyzed the abnormal electrical activity in single cells. Current-clamp and voltage-clamp methods were applied to collagenase digested single myocytes to record the action potential configurations and ionic membrane currents. The dysrhythmias induced by aconitine (modifications of sodium channels) occurred as the abnormal automaticity with spontaneous diastolic depolarization, gradually increased its firing rate (warming up phenomenon) and finally developed to the continuous oscillatory activity. Voltage-clamp study revealed that the amplitude of sodium current decreased and the current voltage relationship shifted to negative potential and the other major ionic currents were barely affected. DADs were induced by ouabain. The higher the concentration of ouabain and more frequency of the stimulation, the amplitude of DADs became more variable and the duration of oscillation became longer. Induction of dysrhythmias at single-cell level might be useful for further understanding and analysis of the ventricular dysrhythmias. (author)