Abstract
An exposure of a biological cell to an electric field results in the induced transmembrane voltage (ITV) proportional to the strength of the electric field and superimposed onto the resting transmembrane voltage for the duration of the exposure. The ITV can have a range of effects from modification of the activity of voltage-gated channels to membrane electroporation, and accurate knowledge of spatial distribution and time course of the ITV is important both for the studies of these phenomena and for effectiveness of their applications. Unlike the resting component of the transmembrane voltage, the induced component varies with position on the membrane, it depends on the shape of the cell and its orientation with respect to the electric field, and in dense cell suspensions and tissues also on the volume fraction occupied by the cells. Inducement of the ITV is a process characterized by a time constant, which amounts to tenths of a microsecond under physiological conditions. As a consequence, the time course of the ITV lags the time course of the electric field that induces it, and for exposures to alternating fields with frequencies above 1 MHz or to pulses with durations below 1 μs, the amplitude of the ITV induced by the field of a given amplitude starts to decrease with further increase of the field frequency or with further decrease of the pulse duration. With field frequencies approaching the GHz range or with pulse durations in the ns range, this attenuation of the ITV comes to a halt, and the voltages induced on the organelle membranes inside the cell can reach the same order of magnitude as the voltage induced by the same field on the plasma membrane, and under certain conditions even exceed it. After the description of methods for analytical derivation and numerical computation of the ITV, the main techniques for experimental determination of ITV are also outlined.
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References
Batista Napotnik T, Reberšek M, Vernier PT, Mali B, Miklavčič D (2016) Effects of high voltage nanosecond electric pulses on eukaryotic cells (in vitro): a systematic review. Bioelectrochemistry 110:1–12. doi:10.1016/j.bioelechem.2016.02.011
Bedlack RS, Wei M, Fox SH, Gross E, Loew LM (1994) Distinct electric potentials in soma and neurite membranes. Neuron 13:1187–1193. doi:10.1016/0896-6273(94)90056-6
Beebe SJ, Fox PM, Rec LJ, Willis EL, Schoenbach KH (2003) Nanosecond, high-intensity pulsed electric fields induce apoptosis in human cells. FASEB J 17:1493–1495. doi:10.1096/fj.02.0859fje
Burnett P, Robertson JK, Palmer JM, Ryan RR, Dubin AE, Zivin RA (2003) Fluorescence imaging of electrically stimulated cells. J Biomol Screen 8:660–667. doi:10.1177/1087057103258546
Cheng DK, Tung L, Sobie EA (1999) Nonuniform responses of transmembrane potential during electric field stimulation of single cardiac cells. Am J Physiol 277:H351–H362
Gimsa J, Wachner D (2001) Analytical description of the transmembrane voltage induced on arbitrarily oriented ellipsoidal and cylindrical cells. Biophys J 81:1888–1896. doi:10.1016/S0006-3495(01)75840-7
Gross D, Loew LM, Webb W (1986) Optical imaging of cell membrane potential changes induced by applied electric fields. Biophys J 50:339–348. doi:10.1016/S0006-3495(86)83467-1
Grosse C, Schwan HP (1992) Cellular membrane potentials induced by alternating fields. Biophys J 63:1632–1642. doi:10.1016/S0006-3495(92)81740-X
Knisley SB, Justice RK, Kong W, Johnson PL (2000) Ratiometry of transmembrane voltage-sensitive fluorescent dye emission in hearts. Am J Physiol Heart Circ Physiol 279:H1421–H1433
Kotnik T, Miklavčič D (2000a) Second-order model of membrane electric field induced by alternating external electric fields. IEEE Trans Biomed Eng 47:1074–1081. doi:10.1109/10.855935
Kotnik T, Miklavčič D (2000b) Analytical description of transmembrane voltage induced by electric fields on spheroidal cells. Biophys J 79:670–679. doi:10.1016/S0006-3495(00)76325-9
Kotnik T, Miklavčič D (2006) Theoretical evaluation of voltage inducement on internal membranes of biological cells exposed to electric fields. Biophys J 90:480–491. doi:10.1529/biophysj.105.070771
Kotnik T, Pucihar G (2010) Induced transmembrane voltage – theory, modeling, and experiments. In: Pakhomov AG, Miklavčič D, Markov MS (eds) Advanced electroporation techniques in biology and medicine. CRC Press, Boca Raton, pp 51–70
Kotnik T, Bobanović F, Miklavčič D (1997) Sensitivity of transmembrane voltage induced by applied electric fields – a theoretical analysis. Bioelectrochem Bioenerg 43:285–291. doi:10.1016/S0302-4598(97)00023-8
Kotnik T, Miklavčič D, Slivnik T (1998) Time course of transmembrane voltage induced by time-varying electric fields – a method for theoretical analysis and its application. Bioelectrochem Bioenerg 45:3–16. doi:10.1016/S0302-4598(97)00093-7
Kotnik T, Pucihar G, Miklavčič D (2010) Induced transmembrane voltage and its correlation with electroporation-mediated molecular transport. J Memb Biol 236:3–13. doi:10.1007/s00232-010-9279-9
Ling G, Gerard RW (1949) The normal membrane potential of frog sartorius fibers. J Cell Comp Physiol 34:383–396
Loew LM (1992) Voltage sensitive dyes: measurement of membrane potentials induced by DC and AC electric fields. Bioelectromagn Suppl 1:179–189. doi:10.1002/bem.2250130717
Lojewska Z, Farkas DL, Ehrenberg B, Loew LM (1989) Analysis of the effect of medium and membrane conductance on the amplitude and kinetics of membrane potentials induced by externally applied electric fields. Biophys J 56:121–128. doi:10.1016/S0006-3495(89)82657-8
Montana V, Farkas DL, Loew LM (1989) Dual-wavelength ratiometric fluorescence measurements of membrane-potential. Biochemistry 28:4536–4539. doi:10.1021/bi00437a003
Neher E, Sakmann B (1976) Single-channel currents recorded from membrane of denervated frog muscle fibres. Nature 260:779–802
Neumann E, Kakorin S, Toensing K (1999) Fundamentals of electroporative delivery of drugs and genes. Bioelectrochem Bioenerg 48:3–16. doi:10.1016/S0302-4598(99)00008-2
Pauly H, Schwan HP (1959) Über die Impedanz einer Suspension von kugelförmigen Teilchen mit einer Schale. Z Naturforsch 14B:125–131
Pavlin M, Pavšelj N, Miklavčič D (2002) Dependence of induced transmembrane potential on cell density, arrangement, and cell position inside a cell system. IEEE Trans Biomed Eng 49:605–612. doi:10.1109/TBME.2002.1001975
Pucihar G, Kotnik T, Valič B, Miklavčič D (2006) Numerical determination of the transmembrane voltage induced on irregularly shaped cells. Ann Biomed Eng 34:642–652. doi:10.1007/s10439-005-9076-2
Pucihar G, Kotnik T, Teissié J, Miklavčič D (2007) Electroporation of dense cell suspensions. Eur Biophys J 36:173–185. doi:10.1007/s00249-006-0115-1
Pucihar G, Miklavčič D, Kotnik T (2009a) A time-dependent numerical model of transmembrane voltage inducement and electroporation of irregularly shaped cells. IEEE T Biomed Eng 56:1491–1501. doi:10.1109/TBME.2009.2014244
Pucihar G, Kotnik T, Miklavčič D (2009b) Measuring the induced membrane voltage with di-8-ANEPPS. J Vis Exp 33:1659. doi:10.3791/1659
Schoenbach KH, Beebe SJ, Buescher ES (2001) Intracellular effect of ultrashort electrical pulses. Bioelectromagnetics 22:440–448. doi:10.1002/bem.71
Susil R, Šemrov D, Miklavčič D (1998) Electric field induced transmembrane potential depends on cell density and organization. Electro Magnetobiol 17:391–399
Tekle E, Oubrahim H, Dzekunov SM, Kolb JF, Schoenbach KH, Chock PB (2005) Selective field effects on intracellular vacuoles and vesicle membranes with nanosecond electric pulses. Biophys J 89:274–284. doi:10.1529/biophysj.104.054494
Valič B, Golzio M, Pavlin M, Schatz A, Faurie C, Gabriel B, Teissié J, Rols MP, Miklavčič D (2003) Effect of electric field induced transmembrane potential on spheroidal cells: theory and experiment. Eur Biophys J 32:519–528. doi:10.1007/s00249-003-0296-9
Zhang J, Davidson RM, Wei MD, Loew LM (1998) Membrane electric properties by combined patch clamp and fluorescence ratio imaging in single neurons. Biophys J 74:48–53. doi:10.1016/S0006-3495(98)77765-3
Acknowledgment
This work was supported by the Slovenian Research Agency (Grant P2-0249) and conducted in the scope of the European Laboratory of Pulsed Electric Fields Applications (LEA EBAM) and within networking efforts of the COST Action TD1104 – European Network for Development of Electroporation-Based Technologies and Treatments (EP4Bio2Med).
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Kotnik, T. (2016). Transmembrane Voltage Induced by Applied Electric Fields. In: Miklavcic, D. (eds) Handbook of Electroporation. Springer, Cham. https://doi.org/10.1007/978-3-319-26779-1_8-1
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DOI: https://doi.org/10.1007/978-3-319-26779-1_8-1
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