Electroporation of skeletal muscle cell membranes has been postulated to cause myonecrosis in victims of major electrical trauma. To evaluate this concept we carried out a series of experiments to measure the transmembrane potential (delta Vm) threshold for skeletal muscle membrane electroporation using isolated mammalian skeletal muscle cells and compared this threshold with the expected range of delta Vm in victims of electrical trauma. Alterations in membrane Mg2+ or Ca2+ permeability in response to applied extracellular field pulses were quantified by measuring the kinetics of influx before and after field exposure. To avoid heating effects, 4-msec duration field pulses were used. The resting intracellular [Mg2+] was 0.86 +/- 0.01 mmol/l, and [Ca2+] was 0.1 +/- 0.01 microns. The delta Vm threshold for transient or stable electropore formation was determined by performing experiments over a wide range of applied fields. A delta Vm of 340 mV produced no significant change in intracellular [Mg2+]. Delta Vms ranging between 340 to 480 mV caused only a transient influx of Mg2+, indicating that spontaneous sealing of the membrane electropores occurred. A delta Vm of greater than 540 mV caused stable electropore formation. In addition, the efficacy of two surface active polymers as membrane sealing agents was tested. Either 1 mmol/L Poloxamer-188 (8.1 kDa) or 1 mmol/L neutral dextran (10.1 kDa) prevented Mg2+ influx after delta Vms greater than 540 mV (p < 0.001, n = 7). These results suggest that the fields produced in victims of electric shock are sufficient to damage cell membranes by a nonthermal mechanism and that nonionic surfactants may rapidly seal electropores.