title: Electroporation-induced inward current in voltage-clamped guinea pig ventricular myocytes.
abstract: 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.
authors.affiliation: Department of Physiology and Biophysics, Dalhousie University, Halifax, NS, B3H 1X5, Canada.
authors.forename: Oksana
authors.initials: O
authors.lastname: Dyachok
authors.forename: Pavel
authors.initials: P
authors.lastname: Zhabyeyev
authors.forename: Terence F
authors.initials: TF
authors.lastname: McDonald
mesh_terms: D000818:Animals; D004594:Electrophysiology; D018274:Electroporation; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D007811:Lanthanum / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*
chemical_list: D007811:Lanthanum