Long QT syndrome type 3 (LQT-3) is a disease related to abnormal cardiac sodium channel function (Nav 1.5), usually due to augmented late sodium current (INaL ), and may lead to ventricular fibrillation. Amiodarone is approved for ventricular fibrillation. Thus, we investigated whether pacing frequency impacts the ability of amiodarone to reverse the arrhythmic phenotype observed in LQT-3. Anemone neurotoxin 2 (ATX-II, here named only ATX) was used to enhance INaL in mice left ventricular myocytes (LVM). A video detector system monitored sarcomere shortening. At 1 Hz, amiodarone attenuated sarcomere shortening only at 10 µmol/L; at 3 and 5 Hz, 0.1 and 1 µmol/L amiodarone also reduced sarcomere shortening. However, no effect of amiodarone was observed on time to 50% of sarcomere contraction and relaxation. In LVM exposed to ATX (10 nmol/L), an arrhythmic phenotype was observed, and it was more severe when cells were paced at 1 Hz. Amiodarone failed to reverse the ATX induced phenotype at different pacing frequencies. Thus, our results suggest that amiodarone's ability to reverse arrhythmias induced by augmentation of INaL is limited. These findings suggest further experimentation will be required to clarify whether a clinical effect can be ascribed to an effect of amiodarone on other ion channels in LQT-3.
Amiodarone/pharmacology , Cardiac Conduction System Disease/drug therapy , Long QT Syndrome/drug therapy , Myocytes, Cardiac/drug effects , Voltage-Gated Sodium Channel Blockers/pharmacology , Amiodarone/therapeutic use , Animals , Cardiac Conduction System Disease/chemically induced , Cardiac Conduction System Disease/physiopathology , Cells, Cultured , Cnidarian Venoms/pharmacology , Disease Models, Animal , Humans , Long QT Syndrome/chemically induced , Long QT Syndrome/physiopathology , Male , Mice , Myocytes, Cardiac/physiology , NAV1.5 Voltage-Gated Sodium Channel/metabolism , Primary Cell Culture , Voltage-Gated Sodium Channel Blockers/therapeutic use
