ASYMMETRICAL ELECTRICALLY-INDUCED INJURY OF RABBIT VENTRICULAR MYOCYTES

Strong defibrillation-type electric field stimulation may injure myocy tes when transmembrane potentials during the pulse exceed the threshol d for membrane permeabilization. The location of injury may depend on intrinsic transmembrane potential or influx of calcium by ''electro-os mosis'' during the stimulation pulse in addition to the transmembrane potential changes induced by the pulse, We have studied injury by exam ining contracture and changes in transmembrane potential-sensitive dye fluorescence induced by electric field stimulation (St) with a durati on of 20 ms and strength of 16-400 V/cm in isolated rabbit ventricular myocytes. St of 100-150 V/cm produced injury in myocytes oriented par allel to the St field frequently without injuring myocytes oriented pe rpendicular to the field, Injury required calcium in the solution and was asymmetric, occurring first at the myocyte end facing the St anode in 100% of injured myocytes in normal Tyrode's solution. Injury depen ded significantly on whether the product of the electric field strengt h and myocyte length exceeded a threshold of 1.1V (P<0.05). Asymmetric injury at the end facing the anode was still present in 96% of injure d myocytes for stimulation after depolarization by an action potential or 20 mM or 125 mM potassium, suggesting that intrinsic transmembrane potential is not responsible for asymmetry. In 125 mM potassium, elim inating calcium from the bathing solution during the St pulse and intr oducing calcium after the pulse decreased the fraction of injured myoc ytes in which injury occurred at the end facing the anode to 62%, sugg esting that calcium influx by ''electro-osmosis'' at the myocyte end f acing the anode contributes to asymmetry. Asymmetric injury at the end facing the anode was still present in 100% of injured myocytes after adding 1 mM tetraethylammonium chloride, indicating that asymmetry is not sensitive to the potassium channel blockade. For stimulation pulse s stronger than 50 V/cm given after depolarization by an action potent ial, transmembrane potentials at both myocyte ends decayed after the i nitial deflection indicating that permeabilization occurred at both en ds. In conclusion, injury depends on myocyte orientation and is asymme tric occurring first at the myocyte end facing the anode. Asymmetric i njury is not explained by asymmetric permeabilization, is independent of the intrinsic transmembrane potential and may result from ''electro -osmosis'' during the stimulation pulse.