Abstract 15625: Flecainide Modulates Action Potential Properties of Cardiac Sympathetic Neurons

Abstract

Introduction: Sympathetic nerve activity is important in the genesis of catecholaminergic polymorphic ventricular tachycardia (CPVT). Flecainide is effective in managing patients with CPVT. Hypothesis: We hypothesize that flecainide in clinically relevant concentrations alters electrical properties of cardiac sympathetic nerves. Methods: We used the perforated-patch technique in current-clamp mode to record action potentials from single sympathetic neurons isolated from stellate and superior cervical ganglia of ∼2-month-old mice. Action potentials in response to current pulses (10 ms, 0.05 to 0.2 nA, 0.2 Hz) were acquired in control, 1, 5, 10 μM flecainide, and wash out. Results: Flecainide dose-dependently decreased action potential amplitude (in mV, medians with 25 and 75% percentiles) from 131.6 [127.0 - 138.0; control] to 131.1 [123.7 - 137.5; 1 μM], 128.9 [120.0 - 134.4; 5 μM] and 126.1 [115.9 - 132.6; 10 μM ; P < 0.05 by Repeated Measures ANOVA], and upstroke dV/dt max (in V/s) from 172 [109 - 216; control] to 158 [110 - 198; 1 μM), 109 [98 - 174; 5 μM) and 92 [84 - 147; 10 μM; P < 0.05]. Action potential duration at 50% repolarization was significantly prolonged at 10 μM flecainide ( P < 0.05). The changes were reversible upon washout. Resting membrane potential was unaltered. The Figure shows representative action potentials for control and 10 μM flecainide. Conclusions: Flecainide-induced changes in action potential properties are compatible with inhibition of neuron-type voltage-gated Na + channels and K + channels. These actions may decrease sympathetic excitability on the heart, thus help control CPVT.