Atrial selectivity in Na 1 channel blockade by acute amiodarone
2013
Na + channel blockers are often used to treat atrial fibrillation (AF), but may sometimes cause ventricular contractile dysfunction. However, amiodarone, a multi-channel blocker with Na + channel block, causes less contractile dysfunc- tion. In this study, we tested the hypothesis that Na + channel block by amiodarone is selective in atrial myocytes (AM) compared with ventricular myocytes (VM). Methods and results Na + currents (INa) were measured using whole-cell patch-clamp technique in isolated rabbit AM and VM. Amiodar- one inhibited INa in AM (IC50: 1.8+1.1 mM; n ¼ 8) much more than in VM (40.4+11.9 mM; n ¼ 7, P , 0.01). Amio- darone at 10 mM shifted the steady-state inactivation relationship in AM (216.2+1.7 mV shift, n ¼ 12) compared with VM (25.9+0.7 mV shift; n ¼ 13; P , 0.01). For mexiletine, the inhibition of INa and inactivation curve shifts were comparable for AM and VM. The effects of amiodarone and mexiletine on conduction velocity (CV) in Langen- dorff-perfused rabbit hearts were evaluated using an optical mapping system. The decrease of CV by 3 mM amiodar- one was significantly larger in the atrium (218.9+3.8% change; n ¼ 5) compared with the ventricle (23.7+3.7%; n ¼ 5; P , 0.01). In contrast, mexiletine reduced CV equally in the atrium and the ventricle. Conclusion Amiodarone preferentially inhibits INa of AM compared with VM. Atrial selective Na + channel block by amiodarone may contribute to treating AF with less effect on ventricular contractility than other Na + channel blockers.
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