Electroporation-induced inward current in voltage-clamped guinea pig ventricular myocytes.

Electroporation induced by high-strength electrical fields has long been used to investigate membrane properties and facilitate transmembrane delivery of molecules and genes for research and clinical purposes. In the heart, electric field-induced passage of ions through electropores is a factor in defibrillation and postshock dysfunction. Voltage-clamp pulses can also induce electroporation, as exemplified by findings in earlier studies on rabbit ventricular myocytes: Long hyperpolarizations to ≤-110 mV induced influx of marker ethidium and irregular inward currents that were as large with external NMDG(+) as Na(+). In the present study, guinea pig ventricular myocytes were bathed with NMDG(+), Na(+) or NMDG(+) + La(3+) solution (36°C) and treated with five channel blockers. Hyperpolarization of myocytes in NMDG(+) solution elicited an irregular inward current (I (ep)) that reversed at -21.5 ± 1.5 mV. In myocytes hyperpolarized with 200-ms steps every 30 s, I (ep) occurred in "episodes" that lasted for one to four steps. Boltzmann fits to data on the incidence of I (ep) per experiment indicate 50% incidence at -129.7 ± 1.4 mV (Na(+)) and -146.3 ± 1.6 mV (NMDG(+)) (slopes ≈-7.5 mV). I (ep) amplitude increased with negative voltage and was larger with Na(+) than NMDG(+) (e.g., -2.83 ± 0.34 vs. -1.40 ± 0.22 nA at -190 mV). La(3+) (0.2 mM) shortened episodes, shifted 50% incidence by -35 mV and decreased amplitude, suggesting that it inhibits opening/promotes closing of electropores. We compare our findings with earlier ones, especially in regard to electropore selectivity. In the Appendix, relative permeabilities and modified excluded-area theory are used to derive estimates of electropore diameters consistent with reversal potential -21.5 mV.