Action Potentials That Mimic Fibrillation Activate Sodium Current

Ventricular fibrillation (VF) has brief action potentials (50–70 ms) with short diastolic intervals (10–30 ms). Under these conditions ion channel activity may be grossly different to normal sinus rhythm (NSR). In particular, sodium channel activation may not contribute to the generation and propagation of action potentials during VF. This study determined if sodium channels can be activated when action potentials mimic VF. Isolated chick ventricular myocytes (n=7) were voltage-clamped to quantitate fast inward sodium current. The voltage clamp protocol simulated VF with a 10 pulse train at 10 Hz (100 ms cycle length (CL)) and depolarization interval (action potential duration) ranging from 90 to 20 ms. After each train a test pulse was delivered from holding (−80 mV) in 10-ms steps. The train preceded each step pulse. Peak sodium current for control and each VF protocol occurred at a membrane potential (Vm) of −10 mV. Sodium current was evident during brief resting intervals as short as 20 ms, albeit 10–20% of baseline. Resting intervals less than 60 ms shifted the sodium conductance activation curve from Vm0.5−30 mV to −22 mV membrane potential. Similar findings occurred when resting potential was at −65 mV, although there was less sodium current with all tested protocols. There was significantly less inactivation of sodium current when the prepulse was shorter (100 v 1000 ms). There was approximately 20% greater sodium current when the test pulse followed a short v long depolarized (>−80 mV) prepulse. Although the longer depolarization pulses produce approximately 20% greater sodium current at membrane potentials more negative than −80 mV. Lastly the time for half recovery of sodium current from activation was significantly less when the inactivating prepulse was short v long (45.9±9 v 118±20 ms,P <0.05). In conclusion, sodium current is evident when the diastolic rest interval is as brief as 10–20 ms. Rest interval, length of membrane depolarization and membrane potential interact to affect sodium channel activation, inactivation and recovery from inactivation. These data demonstrate that the brief action potentials at more depolarized membrane potentials seen during VF allow for inward sodium current upon depolarization, less sodium channel inactivation, and a faster recovery from inactivation, thereby compensating for a short diastolic rest interval. Therefore, it is likely that the inward sodium channel contributes to wave front propagation during ventricular fibrillation.