Injury current modulates afterdepolarizations in single human ventricular cells

Objective: Injury current (I,,) and afterdepolarizations are thought to pla y an important role in arrhythmias that occur during acute ischemia. Howeve r, little is known about the effects of I-injury on afterdepolarizations. T he present study was designed to study the effect of I-injury on afterdepol arizations and action potentials in single human ventricular cells. Methods : The patch-clamp technique was used to record action potentials and to app ly I-injury to human ventricular cells. In these cells, early and delayed a fterdepolarizations (EADs and DADs) were induced by I mu M norepinephrine. I-injury was simulated by coupling cells via a variable coupling resistance to a passive resistance circuit with a potential of 0, -20, or -40 mV, mim icking a depolarized ischemic region. Results: At all potentials, I-injury induced depolarization of the resting membrane potential and action potenti al shortening. Flowing from 0 mV, I-injury induced EADs by itself and aggra vated the EADs and DADs that were induced by norepinephrine. Flowing from - 40 mV, I-injury abolished the noradrenaline-induced EADs and DADs. Conclusi ons: Our results demonstrate that I-injury may either prevent or promote th e occurrence of afterdepolarizations in human ventricle. The latter holds i f conduction is slowed to such an extent that it permits flow of current fr om depolarized ischemic cells at plateau level to cells in phase 3 or phase 4. (C) 2000 Elsevier Science BN. All rights reserved.