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Investigations into the Correlation Properties of Membrane Electroporation-Induced Inward Currents: Prediction of Pore Formation

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Abstract

Membrane electroporation (MEP) induces a drastic change in membrane conductance and permeability. However, the underlying mechanisms by which MEP-induced currents (I MEP) are generated or resealed remain unclear. In this study, we investigated how the fluctuations of I MEP might be elicited in different types of cells, including pituitary GH3 cells, NG108-15 neuronal cells, and RAW 264.7 macrophages. We applied the detrended fluctuation analysis (DFA) to analyze the current signals in response to large hyperpolarizations. The DFA exponents from the current signals at 10 s preceding the start of the initial I MEP (I Pre) in GH3 cells exhibited two components (short time lag [α1] and long time lag [α2]) with a crossover threshold of about 7 ms. The α1 value was 0.46 ± 0.04 (n = 7), whereas the α2 value with 0.62 ± 0.05 (n = 7) indicated the presence of long-term correlations of current signals. However, during maximal I MEP, the slope of double logarithmic plot was linear and estimated to be 0.99 ± 0.02 (n = 8) with no clear crossover. Upon changes in membrane polarization, neither short- nor long-range correlation was altered. Chloroquine (CQ), a lysosomotropic agent, decreased the I MEP amplitude with an IC50 value of 46 μM; however, it had no effects on the scaling exponents of I Pre or I MEP. Although CQ or membrane polarization altered the amplitudes of I MEP, no changes in correlation properties of this current were detected. The scaling exponents derived from I Pre exhibit long-range correlations in these different types of cells, indicating there is a correlated character of the electropore dynamics that may be allowed to predict the MEP process.

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Abbreviations

BKCa channel:

Large-conductance Ca2+-activated K+ channel

CQ:

Chloroquine

DFA:

Detrended fluctuation analysis

DMEM:

Dulbecco’s modified Eagle’s medium

erg :

Ether-à-go-go-related-gene

IC50 :

The concentration required for 50% inhibition

I MEP :

Membrane electroporation-induced current

I Pre :

Current signal obtained at 10 s before the start of I MEP rise

MEP:

Membrane electroporation

SD:

Standard deviation

SEM:

Standard error of mean

SSR:

Sum of squared residuals

References

  1. Koronkiewicz, S., Kalinowski, S., & Bryl, K. (2002). Programmable chronopotentiometry as a tool for the study of electroporation and resealing of pores in bilayer lipid membranes. Biochimica et Biophysica Acta, 1561, 222–229.

    Article  PubMed  CAS  Google Scholar 

  2. Rols, M.-P. (2006). Electropermeabilization, a physical method for the delivery of therapeutic molecules into cells. Biochimica et Biophysica Acta, 1758, 423–428.

    Article  PubMed  CAS  Google Scholar 

  3. Wang, M., Orwar, O., Olofsson, J., & Weber, S. G. (2010). Single-cell electroporation. Analytical and Bioanalytical Chemistry, 397, 3235–3248.

    Article  PubMed  CAS  Google Scholar 

  4. Kanjhan, R., & Vaney, D. I. (2008). Semi-loose seal neurobiotin electroporation for combined structural and functional analysis of neurons. Pflügers Archiv, 457, 561–568.

    Article  PubMed  CAS  Google Scholar 

  5. Lin, Y. C., Li, M., & Wu, C. C. (2004). Simulation and experimental demonstration of the electrical field assisted electroporation microchip for in vitro gene delivery enhancement. Lab on a Chip, 4, 104–108.

    Article  PubMed  CAS  Google Scholar 

  6. Lu, K. Y., Wo, A. M., Lo, Y. J., Chen, K. C., Lin, C. M., & Yang, C. R. (2006). Three dimensional electrode array for cell lysis via electroporation. Biosensors & Bioelectronics, 22, 568–574.

    Article  CAS  Google Scholar 

  7. Peng, C.-K., Havlin, S., Stanley, H. E., & Goldberger, A. L. (1995). Quantification of scaling exponents and crossover phenomena in nonstationary heartbeat time series. Chaos, 5, 82–87.

    Article  PubMed  CAS  Google Scholar 

  8. Varanda, W., Liebovitch, L. S., Figueiroa, J. N., & Nogueira, R. A. (2000). Hurst analysis applied to the study of single calcium-activated potassium channel kinetics. Journal of Theoretical Biology, 206, 343–353.

    Article  PubMed  CAS  Google Scholar 

  9. Siwy, Z., Mercik, S., Weron, K., & Ausloos, M. (2001). Application of dwell-time series in studies of long-range correlation in single channel ion transport: analysis of ion current through a big conductance locust potassium channel. Physica A, 297, 79–96.

    Article  CAS  Google Scholar 

  10. Alvarez-Ramirez, J., Escarela-Perez, R., Espinosa-Perez, G., & Urrea, R. (2009). Dynamics of electricity market correlations. Physica A, 388, 2173–2188.

    Article  Google Scholar 

  11. Ramírez-Rojaz, A., Telesca, L., & Angulo-Brown, F. (2011). Entropy of geoelectrical time series in the natural time domain. Natural Hazards and Earth System Sciences, 11, 219–225.

    Article  Google Scholar 

  12. de Oliveira, R. A. C., Barbosa, C. T. F., Consoni, L. H. A., Rodrigues, A. R. A., Varanda, W. A., & Nogueira, R. A. (2006). Long-term correlation in single calcium-activated potassium channel kinetics. Physica A, 364, 13–22.

    Article  Google Scholar 

  13. Luthman, H., & Magnusson, G. (1983). High efficiency polyoma DNA transfection of chloroquine treated cells. Nucleic Acid Research, 11, 1295–1308.

    Article  CAS  Google Scholar 

  14. Fredericksen, B. L., Wei, B. L., Tao, J., Luo, T., & Garcia, J. V. (2002). Inhibition of endosomal/lysosomal degradation increases the infectivity of human immunodeficiency virus. Journal of Virology, 76, 11440–11446.

    Article  PubMed  CAS  Google Scholar 

  15. Blok, J., Mulder-Stapel, A. A., Ginsel, L. A., & Daems, W. T. (1981). The effect of chloroquine on lysosomal function and cell-coat glycoprotein transport in the absorptive cells of cultured human small-intestinal tissue. Cell and Tissue Research, 218, 227–251.

    Article  PubMed  CAS  Google Scholar 

  16. Perussi, J.-R., Yushmanov, V. E., Monte, S. C., Imasato, H., & Tabak, M. (1995). Interaction of primaquine and chloroquine with ionic micelles as studied by 1H NMR and electronic adsorption spectroscopy. Physiology Chemistry Physical Medicine NMR, 27, 1–15.

    CAS  Google Scholar 

  17. Basso, L. G. M., Rodrigues, R. Z., Naal, R. M. Z. G., & Costa-Filho, A. J. (2011). Effects of the antimalarial drug primaquine on the dynamic structure of lipid model membranes. Biochimica et Biophysica Acta, 1808, 55–64.

    Article  PubMed  CAS  Google Scholar 

  18. Rodríguez-Menchaca, A. A., Navarro-Polanco, R. A., Ferrer-Villada, T., Rupp, J., Sachse, F. B., Tristani-Firouzi, M., et al. (2008). The molecular basis of chloroquine block of the inward rectifier Kir2.1 channel. Proceedings of the National Academy of Sciences of the United States of America, 105, 1364–1368.

    Article  PubMed  Google Scholar 

  19. Wagner, M., Riepe, K. G., Eberhardt, E., & Volk, T. (2010). Open channel block of the fast transient outward K+ current by primaquine and chloroquine in rat left ventricular cardiomyocytes. European Journal of Pharmacology, 647, 13–20.

    Article  PubMed  CAS  Google Scholar 

  20. Honegger, U. E., Quack, G., & Wiesmann, U. N. (1993). Evidence for lysosomotropism of memantine in cultured human cells: Cellular kinetics and effects of memantine on phospholipid content and composition, membrane fluidity and beta-adrenergic transmission. Pharmacology and Toxicology, 73, 202–208.

    Article  PubMed  CAS  Google Scholar 

  21. Wu, S. N., Huang, H. C., Yeh, C. C., Yang, W. H., & Lo, Y. C. (2011). Inhibitory effect of memantine, an NMDA-receptor antagonist, on electroporation-induced inward currents in pituitary GH3 cells. Biochemical and Biophysical Research Communications, 405, 508–513.

    Article  PubMed  CAS  Google Scholar 

  22. Kemmer, G., & Keller, S. (2010). Nonlinear least-squares data fitting in Excel spreadsheets. Nature Protocols, 5, 267–281.

    Article  PubMed  CAS  Google Scholar 

  23. Wood, L. S., Tsai, T., Lee, S. K., & Vogeli, G. (1995). Cloning and functional expression of a human gene, hIRK1, encoding the heart inward rectifier K+-channel. Gene, 163, 313–317.

    Article  PubMed  CAS  Google Scholar 

  24. Clarson, L. H., Greenwood, S. L., Mylona, P., & Sibley, C. P. (2001). Inwardly rectifying K+ current and differentiation of human placental cytotrophoblast cells in culture. Placenta, 22, 328–336.

    Article  PubMed  CAS  Google Scholar 

  25. Liu, Y. C., Wang, Y. J., Wu, P. Y., & Wu, S. N. (2009). Tramadol-induced block of hyperpolarization-activated cation current in rat pituitary lactotrophs. Naunyn-Schmiedebergs Archives of Pharmacology, 379, 127–135.

    Article  CAS  Google Scholar 

  26. Dyachok, O., Zhabyeyev, P., & McDonald, T. F. (2010). Electroporation-induced inward current in voltage-clamped guinea pig ventricular myocytes. Journal of Membrane Biology, 238, 69–80.

    Article  PubMed  CAS  Google Scholar 

  27. Hart, S. L., Collins, L., Gustafsson, K., & Fabre, J. W. (1997). Integrin-mediated transfection with peptides containing arginine-glycine-aspartic acid domains. Gene Therapy, 4, 1225–1230.

    Article  PubMed  CAS  Google Scholar 

  28. Heller, R., Jaroszeski, M., Atkin, A., Moradpour, D., Gilbert, R., Wands, J., et al. (1996). In vivo gene electroinjection and expression in rat liver. FEBS Letters, 389, 225–228.

    Article  PubMed  CAS  Google Scholar 

  29. Higashida, H., Brown, D. A., & Robbins, J. (2000). Both linopiridine- and WAY123,398-sensitive components of IK(M, ng) are modulated by cyclic ADP ribose in NG108-15 cells. Pflügers Archive, 441, 228–234.

    Article  CAS  Google Scholar 

  30. Huang, M. H., Shen, A. Y., Wang, T. S., Wu, H. M., Kang, Y. F., Chen, C. T., et al. (2011). Inhibitory action of methadone and its metabolites on erg-mediated K+ current in GH3 pituitary tumor cells. Toxicology, 280, 1–9.

    Article  PubMed  CAS  Google Scholar 

  31. Pan, M. H., Chang, Y. H., Tsai, M. L., Lai, C. S., Ho, S. Y., Badmaev, V., et al. (2008). Pterostilbene suppressed lipopolysaccharide-induced up-expression of iNOS and COX-2 in murine macrophages. Journal of Agricultural and Food Chemistry, 56, 7502–7509.

    Article  PubMed  CAS  Google Scholar 

  32. Krassowska, W., & Filev, P. D. (2007). Modeling electroporation in a single cell. Biophysical Journal, 92, 404–417.

    Article  PubMed  CAS  Google Scholar 

  33. Wegner, L. H., Flickinger, B., Eing, C., Berghöfer, T., Hohenberger, P., Frey, W., et al. (2011). A patch clamp study on the electro-permeabilization of higher plant cells: supra-physiological voltages induce a high-conductance, K+ selective state of the plasma membrane. Biochimica et Biophysica Acta, 1808(6), 1728–1736.

    Article  PubMed  CAS  Google Scholar 

  34. Tsong, T. Y. (1991). Electroporation of cell membranes. Biophysical Journal, 60, 297–306.

    Article  PubMed  CAS  Google Scholar 

  35. Keil, O., Bojar, H., Prisack, H.-B., & Dall, P. (2001). Novel lipophilic chloroquine analogues for a highly efficient gene transfer into gynecological tumors. Bioorganic & Medicinal Chemistry Letters, 11, 2611–2613.

    Article  CAS  Google Scholar 

  36. Koeberle, M. J., Hughes, P. M., Skellern, G. G., & Wilson, C. G. (2006). Pharmacokinetics and disposition of memantine in the arterially perfused bovine eye. Pharmacology Research, 23, 2781–2798.

    Article  CAS  Google Scholar 

  37. Akuzawa-Tateyama, M., Tateyama, M., & Ochi, R. (1998). Low K+-induced hyperpolarizations trigger transient depolarizations and action potentials in rabbit ventricular myocytes. Journal of Physiology, 513, 775–786.

    Article  PubMed  CAS  Google Scholar 

  38. Wu, S. N., Lo, Y. K., Li, H. F., & Shen, A. Y. (2001). Functional coupling of voltage-dependent L-type Ca2+ current to Ca2+-activated K+ current in pituitary GH3 cells. Chinese Journal of Physiology, 44, 161–167.

    PubMed  Google Scholar 

  39. Brown, M. R., Kronengold, J., Gazula, V.-R., Spilianakis, C. G., Flavell, R. A., von Hehn, C. A. A., et al. (2008). Amino-termini isoforms of the Slack K+ channel, regulated by alternative promoters, differentially modulate rhythmic firing and adaptation. Journal of Physiology, 586, 5161–5179.

    Article  PubMed  CAS  Google Scholar 

  40. Wu, S. N., Peng, H., Chen, B. S., Wang, Y. J., Wu, P. Y., & Lin, M. W. (2008). Potent activation of large-conductance Ca2+-activated K+ channels by the diphenylurea 1,3-bis-[2-hydroxy-5-(trifluoromethyl)phenyl]urea (NS1643) in pituitary tumor (GH3) cells. Molecular Pharmacology, 74, 1696–1704.

    Article  PubMed  CAS  Google Scholar 

  41. Zheng, N., Zhang, X., & Rosania, G. R. (2010). Effect of phospholipidosis on the cellular pharmacokinetics of chloroquine. Journal of Pharmacology and Experimental Therapeutics, 336, 661–671.

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors thank the National Science Council of Taiwan for financial support of this work under contracts (NSC-98-2320-B-006-027-MY3 and NSC-99-2918-I-006-003).

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The authors declare that they have no competing interests.

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Correspondence to Sheng-Nan Wu.

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Wu, SN., Yeh, CC., Wu, PY. et al. Investigations into the Correlation Properties of Membrane Electroporation-Induced Inward Currents: Prediction of Pore Formation. Cell Biochem Biophys 62, 211–220 (2012). https://doi.org/10.1007/s12013-011-9284-3

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