Effect of amiodarone on the expression of myosin isoforms and cellular growth of cardiac muscle cells in culture.

The effect of amiodarone on the expression of myosin isoforms and the growth of neonatal rat cardiac muscle cells in culture was studied by native gel electrophoresis, assays of DNA and protein synthesis, and electron microscopy. Cardiac myocytes exposed to amiodarone in the absence of triiodothyronine (T3) showed predominant V1. When cardiac myocytes were exposed to amiodarone in the presence of T3, they expressed prevalent isomyosin V3, or both V3 and V1 equally. Supraphysiological concentration of T3 counteracted the effect of amiodarone on myocytes, showing the expression of predominant isomyosin V1. Amiodarone has inhibitory effects on DNA synthesis and differentiation of cardiac myocytes. Myocytes treated with amiodarone showed maximum labeling index with 11% labeled cells after day 1. Subsequently, the labeling indexes declined and on the third day ceased, as opposed to the control culture, which attained a peak in labeling index with 60% labeled myocytes on the third day. The labeling indexes declined, showing 11% labeled myocytes at the terminal time point. Myocytes treated with amiodarone lost most of the well-organized myofibrils and other organelles, and instead contained sparse, scattered segments of myofibrils, free myofilaments, many mitochondria with disrupted cristae, and autophagic vacuoles. The results demonstrated that amiodarone has a direct influence on the expression of isomyosin by cardiac myocytes. Furthermore, this drug has inhibitory and degrading effects on the growth and differentiation of cardiac myocytes.