Comparison of the chronic and acute effects of amiodarone on the calcium and potassium currents in rabbit isolated cardiac myocytes

Abstract

1 The acute and chronic effects of amiodarone were studied on the transmembrane ionic currents in rabbit single ventricular myocytes at 35°C by applying the whole-cell configuration of the patch-clamp technique. 2 Acute exposure to 1 and 5 gM amiodarone significantly reduced the amplitude (-53.9 + 3.9%, n = 5 and -64.0+2.0%, n=3, P<0.01), but chronic amiodarone treatment (i.p. 50 mg kg-' day-' for 3-4 weeks) changed neither the amplitude nor the kinetics of the inward calcium current.3 Both acute superfusion with amiodarone (1 and 5 gM) and chronic amiodarone treatment significantly decreased the amplitude of the delayed rectifier outward potassium current (IK). 4 Acute application of amiodarone (1 and 5 gM) did not alter but chronic amiodarone treatment moderately depressed the transient outward current (Ito).5 Neither the acute (1 and 5 gM) nor the chronic amiodarone treatment changed the magnitude of the inward rectifier potassium current (Ikl).6 It is concluded that acute amiodarone application and chronic amiodarone treatment alter transmembrane ionic currents of ventricular myocytes differently. This may explain, at least in part, the marked differences in the cardiac electrophysiological effects observed after acute and chronic amiodarone treatment in patients.

Inhibitory effects of JTV‐519, a novel cardioprotective drug, on potassium currents and experimental atrial fibrillation in guinea‐pig hearts

“…In terms of class III antiarrhythmic drugs, sotalol, E-4031 and dofetilide selectively inhibited I Kr (Sanguinetti & Jurkiewicz, 1990;Jurkiewicz & Sanguinetti, 1993). Amiodarone was also shown to inhibit I Kr in rabbit ventricular cells (Varro et al, 1996) and in Xenopus oocytes expressing the human ether-a-go-gorelated gene (HERG) (Kiehn et al, 1999). In the present study JTV-519 prolonged APD in the absence and presence of muscarinic stimulation.…”

Density and Kinetics of I Kr and I Ks in Guinea Pig and Rabbit Ventricular Myocytes Explain Different Efficacy of I Ks Blockade at High Heart Rate in Guinea Pig and Rabbit

“…15 It prolongs APD by blocking not only I Kr , but also I Ks , 16 I to , 17 I K1 , and sodium channels. 18,19 As with chromanol 293B in guinea pig, considerable prolongation of APD remains at short cycle length.…”

The effect of amiodarone pretreatment on survival of mice with cocaine toxicity

“…Amiodarone is a class III antidysrhythmic drug that primarily affects delayed rectifier potassium currents during phase 3 of depolarization [17]. Amiodarone also blocks sodium channels similar to Ib antidysrhythmics, [18] blocks slow inward calcium currents, [17] and noncompetitively antagonizes α and β-andrenergic receptors [19,20].…”

“…Amiodarone also blocks sodium channels similar to Ib antidysrhythmics, [18] blocks slow inward calcium currents, [17] and noncompetitively antagonizes α and β-andrenergic receptors [19,20]. Theoretically, amiodarone and cocaine could produce synergistic blocking of potassium and calcium channels leading to cardiovascular dysfunction and dysrhythmias.…”