Actions of emigrated neutrophils on Na+ and K+ currents in rat ventricular myocytes

One cytotoxic effect of neutrophils appears to be initiated by enhanced Na+ entry into the myocytes. Thus, manoeuvres that precluded activation of Na+ channels, for example holding the membrane potential at −80 mV, significantly increased the time to cell death or prevented contracture entirely. A mathematical model for the action potential of rat ventricular myocytes has been modified and then utilized to integrate these findings. These simulations demonstrate the marked effects of (50-fold) slowing of the inactivation of 2-4% of the available Na+ channels on action potential duration and the corresponding intracellular Ca2+ transient. In ongoing studies using this combination of approaches, are providing significant new insights into some of the fundamental processes that modulate myocyte damage in acute inflammation.