Abstract
The influence of amiodarone on intracellular transport of calcium ion in cardiomyocytes of rat was investigated. The experiments were performed on isolated papillary muscles of Wistar rats. Force-frequency dependence (0.7, 1, 2, 3, 4 Hz), extrasystolic and postextrasystolic contractions and post-rest (4-60 s) reactions of rat myocardium after amiodarone treatment (1 μM) were investigated. Decay potentiation coefficient of contraction force was estimated. Results. The analyses of force-frequency dependence has shown that amiodarone prevent the decreasing of the force contraction at increasing of the stimulation frequency. Amiodarone promotes increase of the time constant t1(T50), that indicate the drug promotes acceleration of Са2+ transport inside the SR resulting increase of Са2+ in the places of its release from the sarcoplasmic reticulum (SR). Treatment of papillary muscle with amiodarone decreased amplitude of extrasystolic contractions. As known, postextrasystolic and post-rest reactions of myocardium characterize the SR function. We have found amiodarone increased potentiation of postextrasystolic and post-rest contractions. Preliminary caffeine perfusion of muscles preparations cancelled the amiodarone-induced increasing postextrasystolic and post-rest potentiation. However, potentiation decay coefficient before and after treatment with amiodarone didn’t have difference. Conclusions, amiodarone influences on intracellular calcium ions homeostasis by modulation SR functions related with most likely are stipulated either by activation of Са2+ transport from uptake sites to release sites or by prevent of Са2+ leakage from the SR.
Highlights
The wide use of amiodarone in clinical practice is defined by its efficacy and low proarrhythmic activity in comparison with other antiarrhythmic drugs [1,2]
Amiodarone belongs to a class of drugs called Vaughn-Williams Сlass III antiarrhythmic agents, which mechanism of action is stimulated by inhibition of outward potassium channels, leading to prolongation of transmembrane action potential (AP) [3,4]
Contraction amplitude muscles treated with amiodarone at stimulation frequency of 4 Hz corresponded to amplitude of control muscles at stimulation frequency of 1 Hz
Summary
The wide use of amiodarone in clinical practice is defined by its efficacy and low proarrhythmic activity in comparison with other antiarrhythmic drugs [1,2]. Amiodarone belongs to a class of drugs called Vaughn-Williams Сlass III antiarrhythmic agents, which mechanism of action is stimulated by inhibition of outward potassium channels, leading to prolongation of transmembrane action potential (AP) [3,4]. Its pharmacological effects are not restricted with blockade of potassium channel, but have a complex influence on electric parameters of the cardiomyocytes membranes [7]. Chronic use of amiodarone influences on the expression of potassium channels genes [7]. This property of amiodarone could lead to “antiarrhythmic” remodeling of cardiomyocyties. Features of electromechanical coupling organization define dependence between frequency and force of myocardial contraction [17,18,19].
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