A study on the mechanisms of antiarrhythmic agents through gene expression of cardiac potassium channels

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In our present study, we investigated the effects of long-term treatment of amiodarone or varying levels of thyroid hormone on cardiac ion channels, especially repolarizing potassium channels. We also tested possible role of modulation of gene expression on these changes. Firstly, the interaction of amiodarone and thyroid hormone on the cardiac potassium channels were observed in cultured ventricular myocytes isolated from neonatal rat. In the presence of T3, amiodarone at 1 muM decreased both potassium currents of Ito and Ik about 30% within 3-days culture.On the other hand, in the absence of T3, these inhibitory effects on Ito and Ik by amiodarone for 3 days-culture were abolished. Secondly, mRNA levels of cloned K channel subunit, Kv 1.4 and Kv 1.5, were, measured under the various levels of thyroxine, Levels of mRNA of Kv 1.5 was decreased in the hypothyroid condition and increased in hyperthyroid ones. On the other hand, mRNA levels of Kv 1.4 exhibited opposite direction and increased in hypothyroid condition and not affected by hyperthyroid conditions. These result indicate that the inhibitory actions of chronic amiodarone on Ito and Ik were dependent on the levels of thyroid hormones and also suggest that amiodarone exert antiarrhythmic action by counteracting the thyroid hormones due to the interaction to T3 at the cellular levels ion cardiac myocytes.