Spontaneous activity induced in rabbit Purkinje myocytes during coupling to a depolarized model cell.
OBJECTIVE
The development of an "injury current" secondary to heterogeneous ion accumulation and cellular uncoupling across the ischemic border zone has been implicated as a trigger for arrhythmias arising during acute ischemia. The purpose of the present study was to determine the effects of injury current across the Purkinje-ventricular interface in the development of abnormal automaticity.


METHODS
Patch clamp and electronic cell coupling techniques were used to record action potentials from and to apply injury current to isolated rabbit Purkinje myocytes. Injury current was dependent upon: (1) a coupling resistance, which was varied to simulate different degrees of cellular uncoupling, and (2) the difference in Purkinje membrane potential and depolarized ischemic myocardium, which was represented by a passive resistor-capacitor circuit with initial voltages of -70, -60, or -50 mV.


RESULTS
During coupling to the moderately depolarized cell (-60 or -50 mV), Purkinje myocytes developed repetitive, spontaneous activity within a window of coupling resistances. This abnormal automaticity was dependent upon L-type calcium current, as cadmium or nifedipine completely suppressed coupling-induced spontaneous activity.


CONCLUSIONS
Our results demonstrate that injury current alone can induce spontaneous activity in normal Purkinje myocytes. The level of myocardial depolarization and the degree of cellular uncoupling required to induce this activity suggest spontaneous Purkinje activity induced by injury current as a potent trigger for acute ischemic arrhythmias.
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D018920:Coculture Techniques; D017629:Gap Junctions / Q000187:drug effects; D006352:Heart Ventricles; D008094:Lithium / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D017202:Myocardial Ischemia / Q000503:physiopathology*; D009543:Nifedipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011690:Purkinje Fibers / Q000503:physiopathology*; D011817:Rabbits
D002104:Cadmium; D008094:Lithium; D009543:Nifedipine