EFFECTS OF AMIODARONE ON OUABAIN BINDING TO MICROSOMAL NA-ATPASE IN GUINEA-PIG HEART PREPARATIONS(, K+)

1. The influence of amiodarone on [H-3]ouabain (OUA) binding to myocar dial Na+, K+-ATPase was studied at various KCl concentrations in guine a pig heart microsomal preparations to test the hypothesis that the dr ug acts on the same receptor sites as cardiac glycosides. 2. First, a series of assays for OUA binding to Na+, K+-ATPase were performed in t he range of 64-800 nM at 2.5, 5.0 and 10.0 mM K+ concentration. The dr ug exhibited increasing binding tendency with increasing concentration s and elevation in K+ levels, 3. Competitive binding assays were then performed at 256, 512 and 800 nM OUA in the presence of 50, 100 and 20 0 mu M amiodarone at 5.0 mM KCl, respectively. At each OUA concentrati on, a concentration-dependent left to-right shift was observed in the binding affinity with increasing amiodarone concentration. Similar ass ays at 2.5 and 10.0 mM K+ showed the same trends. These effects were s ignificant for 200 mM amiodarone at all K+ levels and OUA concentratio ns. 4. Furthermore, different OUA concentrations were also shown to di splace amiodarone in a concentration-dependent fashion. 5. These resul ts indicate that amiodarone competes with OUA for specific binding sit es on myocardial microsomal Na+, K+-ATPase. They lead to the conclusio n that myocardial Na+, K+-ATPase is a possible receptor for some of th e cardiac actions of amiodarone, such as its proarrhythmic effects. (C ) 1997 Elsevier Science Inc.