Action potentials that mimic fibrillation activate sodium current

Ventricular fibrillation (VF) has brief action potentials (50-70 ms) with s hort diastolic intervals (10-30 ms). Under these conditions ion channel act ivity may be grossly different to normal sinus rhythm (NSR). In particular, sodium channel activation may not contribute to the generation and propaga tion of action potentials during VF. This study determined if sodium channe ls call be activated when action potentials mimic VF. Isolated chick ventri cular myocytes (n = 7) were voltage-clamped to quantitate fast inward sodiu m current, The voltage clamp protocol simulated VF with a 10 pulse train at 10 Hz (100 ms cycle length (CL)) and depolarization interval (action poten tial 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 ste p pulse. Peak sodium current for control and each VF protocol occurred at a membrane potential (V-m) of -10 mV. Sodium current was evident during brie f resting intervals as short as 20 ms, albeit 10-20% of baseline. Resting i nternals less than 60 ms shifted the sodium conductance activation curve fr om Vm(0.5) - 30 mV to -23mV membrane potential. Similar findings occurred w hen resting potential was at -65 mV although there was less sodium current with all tested protocols. There was significantly less inactivation of sod ium current when the prepulse was shorter (100 v 1000 ms), There was approx imately 20% greater sodium current when the test pulse followed a short v l ong depolarized (> - 80 mV) prepulse. Although the longer depolarization pu lses produce approximately 20% greater sodium current at membrane potential s more negative than -80 mV: Lastly the time for half recovery of sodium cu rrent 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, so dium current is evident when the diastolic rest internal is as brief as 10- 20 ms. Rest interval, length of membrane depolarization and membrane potent ial 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 s odium current upon depolarization. less sodium channel inactivation, and a faster recovery from inactivation, thereby compensating for a short diastol ic rest interval. Therefore, it is likely that the inward sodium channel co ntributes to wave front propagation during ventricular fibrillation. (C) 19 99 Academic Press.