Analysis using a modified Luo-Rudy model of ventricular action potentials

To elucidate the subcellular mechanism underlying the after effects of high-intensity DC shocks, a small pore, which mimics reversible dielectric breakdown of the cell membrane (electroporation), was incorporated into a modified Luo-Rudy (L-R) model of ventricular action potentials. In normal myocytes, the pore formation results in a decay of repolarization of the shocked action potential which is followed by prolonged depolarization and oscillation of membrane potential like early after depolarization (EAD). Time- and voltage-dependent changes in delayed-rectifier K/sup +/ current (I/sub k/) in combination with those of L-type Ca/sup 2+/ current (I/sub C/a) and ion flux through the pore (I/sub pore/) are responsible for the prolonged depolarization with EAD-like oscillation of membrane potential. Spontaneous excitation forms the oscillation and depends on an activation of I/sub Ca/. In myocytes of Ca/sup 2+/ overload secondary to 90% inhibition of Na/sup +//K/sup +/ pump, the pore formation results in a delay of repolarization of the shocked action potential, which is followed by slower cyclic depolarization in response to spontaneous release of Ca/sup 2+/ from the sarcoplasmic reticulum (SR). The delay after depolarization (DAD)-type oscillation is abolished by complete block of SR Ca/sup 2+/ release channels. These findings suggest that strong shocks will cause arrhythmogenic responses through a transient rupture of sarcolemma with different subcellular events in ventricular cells under normal and pathological conditions.