AN EXPERIMENTAL-MODEL OF THE PRODUCTION OF EARLY AFTER DEPOLARIZATIONS BY INJURY CURRENT FROM AN ISCHEMIC REGION

An ischemic myocardial region contains cells with a depolarized restin g membrane potential. This depolarization leads to an intercellular cu rrent flow between the ischemic region and the surrounding normal myoc ardial cells which has been termed an ''injury current''. We have devi sed an experimental model system in which an isolated guinea pig ventr icular cell is electrically coupled to a model depolarized cell in ord er to evaluate the effects of this injury current on the electrical pr operties of a normal ventricular cell exposed to drugs which increase calcium current or decrease potassium current. Using low doses of isop roterenol, forskolin, or Bay K 8644 (or 8-bromo-cyclic adenosine monop hosphate in the pipette) we found that the action potential duration o f the isolated cell was lengthened, but that early afterdepolarization s (EADs) were not produced unless the cell was also coupled to a depol arized cell model representing an adjacent ischemic region. A similar prolongation of the action potential was produced by low doses of quin idine, but EADs were not produced unless coupling to a depolarized cel l model was added. EADs could not be produced in any cells in the abse nce of the drugs even though the coupling to the depolarized cell mode l was increased up to the level at which the action potential was inde finitely prolonged. At higher isoproterenol concentrations, EADs or sp ontaneous activity were produced without coupling to the depolarized c ell model. Under these conditions, coupling of the cell to a cell mode l with normal resting membrane potential stopped the spontaneous activ ity and prevented the occurrence of EADs even with high levels of resi stive coupling. These findings suggest that the electrotonic influence s of a localized depolarized region can produce EADs if the calcium cu rrent magnitude is increased, which would be the case for sympathetic innervation.