Bioelectric mechanisms in regeneration: Unique aspects and future perspectives

Seminars in Cell and Developmental Biology

Volumn 20, Issue 5, 2009, Pages 543-556

  Levin, Michael ^a  

^a TUFTS UNIVERSITY   (United States)

Author keywords

Bioelectricity; Ion channel; Regeneration; Transmembrane potential

Indexed keywords

BIOENERGY; CELL DIFFERENTIATION; CELL MIGRATION; CELL PROLIFERATION; ELECTRIC FIELD; ELECTRIC POTENTIAL; FEEDBACK SYSTEM; HUMAN; ION CURRENT; MEMBRANE POTENTIAL; MORPHOGENESIS; NONHUMAN; REGENERATION; REVIEW; SIGNAL TRANSDUCTION;

EID: 67649429784     PISSN: 10849521     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.semcdb.2009.04.013     Document Type: Review

References (251)

1. Borgens R.B. The role of natural and applied electric fields in neuronal regeneration and development. Prog Clin Biol Res 210 (1986) 239-250
2. Borgens R.B., Blight A.R., and Murphy D.J. Axonal regeneration in spinal cord injury: a perspective and new technique. J Comp Neurol 250 (1986) 157-167
3. Borgens R.B., Blight A.R., and McGinnis M.E. Functional recovery after spinal cord hemisection in guinea pigs: the effects of applied electric fields. J Comp Neurol 296 (1990) 634-653
4. Bentrup F., Sandan T., and Jaffe L. Induction of polarity in fucus eggs by potassium ion gradients. Protoplasma 64 (1967) 254
5. Novák B., and Bentrup F.W. An electrophysiological study of regeneration in Acetabularia Mediterranea. Planta 108 (1972) 227-244
6. Novak B., and Sirnoval C. Inhibition of regeneration of Acetabularia mediterranea enucleated posterior stalk segments by electrical isolation. Plant Sci Lett 5 (1975) 183-188
7. Cone C.D., and Tongier M. Control of somatic cell mitosis by simulated changes in the transmembrane potential level. Oncology 25 (1971) 168-182
8. Cone C.D., and Tongier M. Contact inhibition of division: involvement of the electrical transmembrane potential. J Cell Physiol 82 (1973) 373-386
9. McCaig C.D., Rajnicek A.M., Song B., and Zhao M. Controlling cell behavior electrically: current views and future potential. Physiol Rev 85 (2005) 943-978
10. Jaffe L.A., and Schlichter L.C. Fertilization-induced ionic conductances in eggs of the frog, Rana pipiens. J Physiol 358 (1985) 299-319
11. Grey R.D., Bastiani M.J., Webb D.J., and Schertel E.R. An electrical block is required to prevent polyspermy in eggs fertilized by natural mating of Xenopus laevis. Dev Biol 89 (1982) 475-484
12. Borgens R., Robinson K., Vanable J., and McGinnis M. Electric Fields in Vertebrate Repair (1989), Alan R. Liss, New York
13. Jaffe L. In: Subtelny S. (Ed). Developmental Order: its origin and regulation (1982), Alan R Liss, New York 183-215
14. Rose S.M. Bioelectric Control of Regeneration in Tubularia. Am Zool 14 (1974) 797-803
15. Marsh G., and Beams H. Electrical control of morphogenesis in regenerating dugesia tigrina. J Cell Comp Physiol 39 (1957) 191-211
16. Rose S.M. Correlation between bioelectrical and morphogenetic polarity during regeneration in tubularia. Dev Biol 28 (1972) 274
17. Dimmitt J., and Marsh G. Electrical control of morphogenesis in regenerating dugesia-tigrina. 2. Potential gradient Vs current density as control factors. J Cell Comp Physiol 40 (1952) 11-23
18. Marsh G., and Beams H.W. Electrical control of growth axis in a regenerating annelid. Anat Rec 108 (1950) 512-612
19. Marsh G., and Beams H.W. Electrical control of morphogenesis in regenerating dugesia tigrina. 1. Relation of axial polarity to field strength. J Cell Comp Physiol 39 (1952) 191
20. Robinson K.R. Electric fields in vertebrate repair (1989), Alan R. Liss pp. 1-25
21. Fitzharris G., and Baltz J.M. Granulosa cells regulate intracellular pH of the murine growing oocyte via gap junctions: development of independent homeostasis during oocyte growth. Development 133 (2006) 591-599
22. Mathews A.P. Electrical polarity in the hydroids. Am J Physiol 8 (1903) 294-299
23. Lund E. Bioelectric fields and growth (1947), Univ. of Texas Press, Austin
24. Burr H.S. The meaning of bioelectric potentials. Yale J Biol Med 16 (1944) 353
25. Burr H.S., and Northrop F. The electrodynamic theory of life. Quart Rev Biol 10 (1935) 322-333
26. Slack J.M. In: Subtelny S. (Ed). Developmental order: its origin and regulation (1982), Alan R. Liss, New York pp. 423-436
27. Marsh G., and Beams H.W. Electrical control of axial polarity in a regenerating annelid. Anat Rec 105 (1949) 513-514
28. Marsh G., and Beams H.W. Electrical control of growth polarity in regenerating dugesia-tigrina. Fed Proc 6 (1947) 163-164
29. Nuccitelli R. Vibrating probe-high spatial-resolution extracellular current measurement. Fed Proc 39 (1980) 2129-2229
30. Jaffe L.F., and Nuccitelli R. An ultrasensitive vibrating probe for measuring steady extracellular currents. J Cell Biol 63 (1974) 614-628
31. Jaffe L.F., and Nuccitelli R. Electrical controls of development. Ann Rev Biophys Bioeng 6 (1977) 445-476
32. Jaffe L. The role of ionic currents in establishing developmental pattern. Philos Trans Roy Soc (Series B) 295 (1981) 553-566
33. Nuccitelli R. Endogenous ionic currents and DC electric-fields in multicellular animal-tissues. Bioelectromagnetics (1992) 147-157
34. Hotary K.B., and Robinson K.R. Endogenous electrical currents and voltage gradients in Xenopus embryos and the consequences of their disruption. Dev Biol 166 (1994) 789-800
35. Robinson K.R., and Messerli M.A. In: McCaig C.D. (Ed). Nerve Growth and Guidance (1996), Portland Press, London pp. 131-150
36. Borgens R.B. What is the role of naturally produced electric current in vertebrate regeneration and healing. Int Rev Cytol 76 (1982) 245-298
37. Borgens R.B. The role of ionic current in the regeneration and development of the amphibian limb. Prog Clin Biol Res 110 Pt A (1983) 597-608
38. Rajnicek A.M., Foubister L.E., and McCaig C.D. Growth cone steering by a physiological electric field requires dynamic microtubules, microfilaments and Rac-mediated filopodial asymmetry. J Cell Sci 119 (2006) 1736-1745
39. Rajnicek A.M., Foubister L.E., and McCaig C.D. Prioritising guidance cues: directional migration induced by substratum contours and electrical gradients is controlled by a rho/cdc42 switch. Dev Biol 312 (2007) 448-460
40. Zhao M., Dick A., Forrester J.V., and McCaig C.D. Electric field-directed cell motility involves up-regulated expression and asymmetric redistribution of the epidermal growth factor receptors and is enhanced by fibronectin and laminin. Mol Biol Cell 10 (1999) 1259-1276
41. Zhao M., Song B., Pu J., Wada T., Reid B., Tai G., et al. Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-gamma and PTEN. Nature 442 (2006) 457-460
42. Zhao M., Forrester J.V., and McCaig C.D. A small, physiological electric field orients cell division. Proc Natl Acad Sci USA 96 (1999) 4942-4946
43. Sundelacruz S., Levin M., and Kaplan D.L. Membrane potential controls adipogenic and osteogenic differentiation of mesenchymal stem cells. PLoS ONE 3 (2008) e3737
44. Nogi T., and Levin M. Characterization of innexin gene expression and functional roles of gap-junctional communication in planarian regeneration. Dev Biol 287 (2005) 314-335
45. Oviedo N.J., and Levin M. Smedinx-11 is a planarian stem cell gap junction gene required for regeneration and homeostasis. Development 134 (2007) 3121-3131
46. +-ATPase and cell membrane potentials comprise a very early step in left-right patterning. Cell 111 (2002) 77-89
47. +-V-ATPase-dependent proton flux is necessary for consistent left-right patterning of non-mammalian vertebrates. Development 133 (2006) 1657-1671
48. + pump-dependent changes in membrane voltage are an early mechanism necessary and sufficient to induce Xenopus tail regeneration. Development 134 (2007) 1323-1335
49. Morokuma J., Blackiston D., Adams D.S., Seebohm G., Trimmer B., and Levin M. Modulation of potassium channel function confers a hyperproliferative invasive phenotype on embryonic stem cells. Proc Natl Acad Sci USA 105 (2008) 16608-16613
50. Stuhmer W., Alves F., Hartung F., Zientkowska M., and Pardo L.A. Potassium channels as tumour markers. FEBS Lett 580 (2006) 2850-2852
51. Arcangeli A., Crociani O., Lastraioli E., Masi A., Pillozzi S., and Becchetti A. Targeting ion channels in cancer: a novel frontier in antineoplastic therapy. Curr Med Chem 16 (2009) 66-93
52. Simons M., Gault W.J., Gotthardt D., Rohatgi R., Klein T.J., Shao Y., et al. Electrochemical cues regulate assembly of the Frizzled/Dishevelled complex at the plasma membrane during planar epithelial polarization. Nat Cell Biol 11 (2009) 286-294
53. Aw S., and Levin M. Is left-right asymmetry a form of planar cell polarity?. Development 136 (2009) 355-366
54. Nuccitelli R. A role for endogenous electric fields in wound healing. Curr Top Dev Biol 58 (2003) 1-26
55. Huttenlocher A., and Horwitz A.R. Wound healing with electric potential. N Engl J Med 356 (2007) 303-304
56. Reid B., Song B., McCaig C.D., and Zhao M. Wound healing in rat cornea: the role of electric currents. FASEB J 19 (2005) 379-386
57. Kunzelmann K. Ion channels and cancer. J Membr Biol 205 (2005) 159-173
58. Lang F., Foller M., Lang K., Lang P., Ritter M., Vereninov A., et al. Cell volume regulatory ion channels in cell proliferation and cell death. Methods Enzymol 428 (2007) 209-225
59. Lang F., Foller M., Lang K.S., Lang P.A., Ritter M., Gulbins E., et al. Ion channels in cell proliferation and apoptotic cell death. J Membr Biol 205 (2005) 147-157
60. Wonderlin W.F., and Strobl J.S. Potassium channels, proliferation and G1 progression. J Membr Biol 154 (1996) 91-107
61. Levin M. Large-scale biophysics: ion flows and regeneration. Trends Cell Biol 17 (2007) 262-271
62. Bryant P.J., Bryant S.V., and French V. Biological regeneration and pattern formation. Sci Am 237 (1977) 66-76
63. French V., Bryant P.J., and Bryant S.V. Pattern regulation in epimorphic fields. Science 193 (1976) 969-981
64. Barkai N., and Ben-Zvi D. 'Big frog, small frog'-maintaining proportions in embryonic development. FEBS J 276 (2009) 1196-1207
65. Slack J.M. A serial threshold theory of regeneration. J Theor Biol 82 (1980) 105-140
66. Oviedo N.J., Newmark P.A., and Sanchez Alvarado A. Allometric scaling and proportion regulation in the freshwater planarian Schmidtea mediterranea. Dev Dyn 226 (2003) 326-333
67. Butler E.G., and O'Brien J.P. Effects of localized X-irradiation on regeneration of the Urodele limb. Anat Rec 84 (1942) 407-413
68. Farinella-Ferruzza N. The transformation of a tail into a limb after xenoplastic transformation. Experientia 15 (1956) 304-305
69. Farinella-Ferruzza N. Risultati di trapianti di bottone codale di urodeli su anuri e vice versa. Riv Biol 45 (1953) 523-527
70. Guyenot E. Le probleme morphogenetique dans la regeneration des urodeles: determination et potentialites des regenerats. Rev Suisse Zool 34 (1927) 127-155
71. Guyenot E., and Schotte O.E. Greffe de regenerat et differenciation induite. Comptes Rendus de Societe de Phys His Nat Geneve 44 (1927) 21-23
72. Beloussov L.V., Opitz J.M., and Gilbert S.F. Life of Alexander G. Gurwitsch and his relevant contribution to the theory of morphogenetic fields. Int J Dev Biol 41 (1997) 771-777 comment 78-9
73. Martinez-Frias M.L., Frias J.L., and Opitz J.M. Errors of morphogenesis and developmental field theory. Am J Med Genet 76 (1998) 291-296
74. Beloussov L.V. Morphogenetic fields: outlining the alternatives and enlarging the context. Riv Biol 94 (2001) 219-235
75. Schiffmann Y. The second messenger system as the morphogenetic field. Biochem Biophys Res Commun 165 (1989) 1267-1271
76. Schiffmann Y. An hypothesis: phosphorylation fields as the source of positional information and cell differentiation-(cAMP, ATP) as the universal morphogenetic Turing couple. Prog Biophys Mol Biol 56 (1991) 79-105
77. Lewis J. From signals to patterns: space, time, and mathematics in developmental biology. Science 322 (2008) 399-403
78. Driesch H. The science & philosophy of the organism. 2nd ed. (1929), A. & C. Black, London pp. xii, 344
79. Child C.M. Patterns and problems of development (1941), The University of Chicago press, Chicago, IL pp. ix, 811
80. Spemann H. Embryonic development and induction. Mrs. Hepsa Ely Silliman Memorial Lectures [1933] (1938), Yale University Press, H. Milford Oxford University Press, New Haven pp. xii, 401
81. Weiss P.A. Principles of development; a text in experimental embryology (1939), H. Holt and Company, New York 601 pp
82. Tataria M., Perryman S.V., and Sylvester K.G. Stem cells: tissue regeneration and cancer. Semin Pediatr Surg 15 (2006) 284-292
83. White R.M., and Zon L.I. Melanocytes in development, regeneration, and cancer. Cell Stem Cell 3 (2008) 242-252
84. Tsonis P.A. Embryogenesis and carcinogenesis: order and disorder. Anticancer Res 7 (1987) 617-623
85. Donaldson D.J., and Mason J.M. Cancer-related aspects of regeneration research: a review. Growth 39 (1975) 475-496
86. Lee M., and Vasioukhin V. Cell polarity and cancer-cell and tissue polarity as a non-canonical tumor suppressor. J Cell Sci 121 (2008) 1141-1150
87. Klezovitch O., Fernandez T.E., Tapscott S.J., and Vasioukhin V. Loss of cell polarity causes severe brain dysplasia in Lgl1 knockout mice. Genes Dev 18 (2004) 559-571
88. Zhan L., Rosenberg A., Bergami K.C., Yu M., Xuan Z., Jaffe A.B., et al. Deregulation of scribble promotes mammary tumorigenesis and reveals a role for cell polarity in carcinoma. Cell 135 (2008) 865-878
89. Zallen J.A. Planar polarity and tissue morphogenesis. Cell 129 (2007) 1051-1063
90. Bryant S.V., Fyfe D., and Singer M. The effects of denervation on the ultrastructure of young limb regenerates in the newt, Triturus. Dev Biol 24 (1971) 577-595
91. Maden M. Neurotrophic control of the cell cycle during amphibian limb regeneration. J Embryol Exp Morphol 48 (1978) 169-175
92. Yntema C.L. Blastema formation in sparsely innervated and aneurogenic forelimbs of amblystoma larvae. J Exp Zool 142 (1959) 423-439
93. Sollars S.I., Smith P.C., and Hill D.L. Time course of morphological alterations of fungiform papillae and taste buds following chorda tympani transection in neonatal rats. J Neurobiol 51 (2002) 223-236
94. Han I.S., Seo T.B., Kim K.H., Yoon J.H., Yoon S.J., and Namgung U. Cdc2-mediated Schwann cell migration during peripheral nerve regeneration. J Cell Sci 120 (2007) 246-255
95. Salo E., and Baguna J. Cell movement in intact and regenerating planarians. Quantitation using chromosomal, nuclear and cytoplasmic markers. J Embryol Exp Morphol 89 (1985) 57-70
96. Zupanc G.K. Neurogenesis and neuronal regeneration in the adult fish brain. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 192 (2006) 649-670
97. Chute J.P. Stem cell homing. Curr Opin Hematol 13 (2006) 399-406
98. Anderson J.D. Galvanotaxis of slime mold. J Gen Physiol 35 (1951) 1-16
99. Hyman L., and Bellamy A. Studies on the correlation between metabolic gradients, electrical gradients, and galvanotaxis I. Biol Bull XLIII (1922) 313-347
100. Song B., Gu Y., Pu J., Reid B., Zhao Z., and Zhao M. Application of direct current electric fields to cells and tissues in vitro and modulation of wound electric field in vivo. Nat Protoc 2 (2007) 1479-1489
101. Robinson K.R., and Cormie P. Electric field effects on human spinal injury: is there a basis in the in vitro studies?. Dev Neurobiol 68 (2008) 274-280
102. Borgens R., Metcalf M., and Shi R. Endogenous ionic currents and voltages in amphibian embryos. J Exp Zool 268 (1994) 307-322
103. Hotary K.B., and Robinson K.R. The neural tube of the Xenopus embryo maintains a potential difference across itself. Brain Res Dev Brain Res 59 (1991) 65-73
104. Stump R.F., and Robinson K.R. Xenopus neural crest cell migration in an applied electrical field. J Cell Biol 97 (1983) 1226-1233
105. Zhao M., McCaig C.D., Agius-Fernandez A., Forrester J.V., and Araki-Sasaki K. Human corneal epithelial cells reorient and migrate cathodally in a small applied electric field. Curr Eye Res 16 (1997) 973-984
106. Pullar C.E., and Isseroff R.R. Cyclic AMP mediates keratinocyte directional migration in an electric field. J Cell Sci 118 (2005) 2023-2034
107. Nishimura K.Y., Isseroff R.R., and Nuccitelli R. Human keratinocytes migrate to the negative pole in direct current electric fields comparable to those measured in mammalian wounds. J Cell Sci 109 Pt 1 (1996) 199-207
108. Shi R., and Borgens R.B. Three-dimensional gradients of voltage during development of the nervous system as invisible coordinates for the establishment of embryonic pattern. Dev Dyn 202 (1995) 101-114
109. Yan X., Han J., Zhang Z., Wang J., Cheng Q., Gao K., et al. Lung cancer A549 cells migrate directionally in DC electric fields with polarized and activated EGFRs. Bioelectromagnetics 30 (2009) 29-35
110. Mycielska M.E., and Djamgoz M.B. Cellular mechanisms of direct-current electric field effects: galvanotaxis and metastatic disease. J Cell Sci 117 (2004) 1631-1639
111. Fraser S.P., Diss J.K., Chioni A.M., Mycielska M.E., Pan H., Yamaci R.F., et al. Voltage-gated sodium channel expression and potentiation of human breast cancer metastasis. Clin Cancer Res 11 (2005) 5381-5389
112. Schwab A. Function and spatial distribution of ion channels and transporters in cell migration. Am J Physiol Renal Physiol 280 (2001) F739-F747
113. Schwab A., Gabriel K., Finsterwalder F., Folprecht G., Greger R., Kramer A., et al. Polarized ion transport during migration of transformed Madin-Darby canine kidney cells. Pflugers Arch 430 (1995) 802-807
114. Barth L.G., and Barth L.J. Ionic regulation of embryonic induction and cell differentiation in Rana pipiens. Dev Biol 39 (1974) 1-22
115. Barth L.J., and Barth L.G. Effect of the potassium ion on induction of notochord from gastrula ectoderm of Rana pipiens. Biol Bull 146 (1974) 313-325
116. Park K.S., Jung K.H., Kim S.H., Kim K.S., Choi M.R., Kim Y., et al. Functional expression of ion channels in mesenchymal stem cells derived from umbilical cord vein. Stem Cells 25 (2007) 2044-2052
117. Flanagan L.A., Lu J., Wang L., Marchenko S.A., Jeon N.L., Lee A.P., et al. Unique dielectric properties distinguish stem cells and their differentiated progeny. Stem Cells 26 (2008) 656-665
118. Balana B., Nicoletti C., Zahanich I., Graf E.M., Christ T., Boxberger S., et al. 5-Azacytidine induces changes in electrophysiological properties of human mesenchymal stem cells. Cell Res 16 (2006) 949-960
119. Chafai M., Louiset E., Basille M., Cazillis M., Vaudry D., Rostene W., et al. PACAP and VIP promote initiation of electrophysiological activity in differentiating embryonic stem cells. Ann N Y Acad Sci 1070 (2006) 185-189
120. Ravens U. Electrophysiological properties of stem cells. Herz 31 (2006) 123-126
121. Wenisch S., Trinkaus K., Hild A., Hose D., Heiss C., Alt V., et al. Immunochemical, ultrastructural and electrophysiological investigations of bone-derived stem cells in the course of neuronal differentiation. Bone 38 (2006) 911-921
122. Biagiotti T., D'Amico M., Marzi I., Di Gennaro P., Arcangeli A., Wanke E., et al. Cell renewing in neuroblastoma: electrophysiological and immunocytochemical characterization of stem cells and derivatives. Stem Cells (2005) [E-pub ahead of print]
123. Wang K., Xue T., Tsang S.Y., Van Huizen R., Wong C.W., Lai K.W., et al. Electrophysiological properties of pluripotent human and mouse embryonic stem cells. Stem Cells 23 (2005) 1526-1534
124. 2+ signals to human myoblast differentiation and fusion. Development 133 (2006) 3107-3114
125. Harrington D.B., and Becker R.O. Electrical stimulation of RNA and protein synthesis in the frog erythrocyte. Exp Cell Res 76 (1973) 95-98
126. Cone C.D., and Cone C.M. Induction of mitosis in mature neurons in central nervous system by sustained depolarization. Science 192 (1976) 155-158
127. Stillwell E.F., Cone C.M., and Cone C.D. Stimulation of DNA synthesis in CNS neurones by sustained depolarisation. Nat New Biol 246 (1973) 110-111
128. Binggeli R., and Weinstein R. Membrane potentials and sodium channels: hypotheses for growth regulation and cancer formation based on changes in sodium channels and gap junctions. J Theor Biol 123 (1986) 377-401
129. MacFarlane S.N., and Sontheimer H. Changes in ion channel expression accompany cell cycle progression of spinal cord astrocytes. Glia 30 (2000) 39-48
130. + channels in the quercetin-induced inhibition of neuroblastoma cell growth. Pflugers Arch 423 (1993) 202-205
131. Cone C.D. The role of the surface electrical transmembrane potential in normal and malignant mitogenesis. Ann NY Acad Sci 238 (1974) 420-435
132. Arcangeli A., Carla M., Bene M., Becchetti A., Wanke E., and Olivotto M. Polar/apolar compounds induce leukemia cell differentiation by modulating cell-surface potential. PNAS 90 (1993) 5858-5862
133. Valenzuela S.M., Mazzanti M., Tonini R., Qiu M.R., Warton K., Musgrove E.A., et al. The nuclear chloride ion channel NCC27 is involved in regulation of the cell cycle. J Physiol 529 Pt 3 (2000) 541-552
134. + channel expression in human breast cancer cells: involvement in cell cycle regulation and carcinogenesis. J Membr Biol 221 (2008) 1-6
135. Putney L.K., and Barber D.L. Na-H exchange-dependent increase in intracellular pH times G2/M entry and transition. J Biol Chem 278 (2003) 44645-44649
136. Boutillier A.L., Kienlen-Campard P., and Loeffler J.P. Depolarization regulates cyclin D1 degradation and neuronal apoptosis: a hypothesis about the role of the ubiquitin/proteasome signalling pathway. Eur J Neurosci 11 (1999) 441-448
137. Nuckels R.J., Ng A., Darland T., and Gross J.M. The vacuolar-ATPase complex regulates retinoblast proliferation and survival, photoreceptor morphogenesis, and pigmentation in the zebrafish eye. Invest Ophthalmol Vis Sci 50 (2009) 893-905
138. Certal A.C., Almeida R.B., Carvalho L.M., Wong E., Moreno N., Michard E., et al. Exclusion of a proton ATPase from the apical membrane is associated with cell polarity and tip growth in Nicotiana tabacum pollen tubes. Plant Cell 20 (2008) 614-634
139. Zupanc M.M., Wellbrock U.M., and Zupanc G.K. Proteome analysis identifies novel protein candidates involved in regeneration of the cerebellum of teleost fish. Proteomics 6 (2006) 677-696
140. Hwang J.S., Kobayashi C., Agata K., Ikeo K., and Gojobori T. Detection of apoptosis during planarian regeneration by the expression of apoptosis-related genes and TUNEL assay. Gene 333 (2004) 15-25
141. Nadal-Ginard B., Kajstura J., Anversa P., and Leri A. A matter of life and death: cardiac myocyte apoptosis and regeneration. J Clin Invest 111 (2003) 1457-1459
142. Mescher A.L., White G.W., and Brokaw J.J. Apoptosis in regenerating and denervated, nonregenerating urodele forelimbs. Wound Repair Regen 8 (2000) 110-116
143. Wang L., Zhou P., Craig R.W., and Lu L. Protection from cell death by mcl-1 is mediated by membrane hyperpolarization induced by K(+) channel activation. J Membr Biol 172 (1999) 113-120
144. Gilbert M.S., Saad A.H., Rupnow B.A., and Knox S.J. Association of BCL-2 with membrane hyperpolarization and radioresistance. J Cell Physiol 168 (1996) 114-122
145. + channel, a regulator of tumor cell apoptosis and proliferation. Cancer Res 62 (2002) 4843-4848
146. + channel in malignant astrocytoma cell lines. J Neurosci Res 48 (1997) 122-127
147. + channels in cell survival and differentiation in the endocrine pancreas. Diabetes 50 Suppl 1 (2001) S48-51
148. Miki T., Tashiro F., Iwanaga T., Nagashima K., Yoshitomi H., Aihara H., et al. Abnormalities of pancreatic islets by targeted expression of a dominant-negative KATP channel. Proc Natl Acad Sci USA 94 (1997) 11969-11973
149. Lauritzen I., De Weille J.R., and Lazdunski M. The potassium channel opener (-)-cromakalim prevents glutamate-induced cell death in hippocampal neurons. J Neurochem 69 (1997) 1570-1579
150. + channels. J Biol Chem 278 (2003) 32068-32076
151. Tseng A.S., Adams D.S., Qiu D., Koustubhan P., and Levin M. Apoptosis is required during early stages of tail regeneration in Xenopus laevis. Dev Biol 301 (2007) 62-69
152. Levin M. Gap junctional communication in morphogenesis. Prog Biophys Mol Biol 94 (2007) 186-206
153. Nicholson B.J. Gap junctions-from cell to molecule. J Cell Sci 116 (2003) 4479-4481
154. Cooper M.S. Gap junctions increase the sensitivity of tissue cells to exogenous electric fields. J Theor Biol 111 (1984) 123-130
155. Russo R.E., Reali C., Radmilovich M., Fernandez A., and Trujillo-Cenoz O. Connexin 43 delimits functional domains of neurogenic precursors in the spinal cord. J Neurosci 28 (2008) 3298-3309
156. + channels in EGF-stimulated alveolar epithelial cell repair processes. Am J Physiol Lung Cell Mol Physiol 293 (2007) L870-L882
157. Chao P.H., Lu H.H., Hung C.T., Nicoll S.B., and Bulinski J.C. Effects of applied DC electric field on ligament fibroblast migration and wound healing. Connect Tissue Res 48 (2007) 188-197
158. Raja, Sivamani K., Garcia M.S., and Isseroff R.R. Wound re-epithelialization: modulating keratinocyte migration in wound healing. Front Biosci 12 (2007) 2849-2868
159. Chifflet S., Hernandez J.A., and Grasso S. A possible role for membrane depolarization in epithelial wound healing. Am J Physiol Cell Physiol 288 (2005) C1420-C1430
160. Chifflet S., Hernandez J.A., Grasso S., and Cirillo A. Nonspecific depolarization of the plasma membrane potential induces cytoskeletal modifications of bovine corneal endothelial cells in culture. Exp Cell Res 282 (2003) 1-13
161. Borgens R.B., Toombs J.P., Breur G., Widmer W.R., Waters D., Harbath A.M., et al. An imposed oscillating electrical field improves the recovery of function in neurologically complete paraplegic dogs. J Neurotrauma 16 (1999) 639-657
162. Borgens R.B., Blight A.R., and McGinnis M.E. Behavioral recovery induced by applied electric fields after spinal cord hemisection in guinea pig. Science 238 (1987) 366-369
163. Borgens R.B., Roederer E., and Cohen M.J. Enhanced spinal cord regeneration in lamprey by applied electric fields. Science 213 (1981) 611-617
164. Shapiro S., Borgens R., Pascuzzi R., Roos K., Groff M., Purvines S., et al. Oscillating field stimulation for complete spinal cord injury in humans: a phase 1 trial. J Neurosurg Spine 2 (2005) 3-10
165. Smith S.D. Effects of electrical fields upon regeneration in the metazoa. Am Zool 10 (1970) 133-140
166. Borgens R.B. Are limb development and limb regeneration both initiated by an integumentary wounding? A hypothesis. Differentiation 28 (1984) 87-93
167. Borgens R.B., McGinnis M.E., Vanable Jr. J.W., and Miles E.S. Stump currents in regenerating salamanders and newts. J Exp Zool 231 (1984) 249-256
168. Jenkins L.S., Duerstock B.S., and Borgens R.B. Reduction of the current of injury leaving the amputation inhibits limb regeneration in the red spotted newt. Dev Biol 178 (1996) 251-262
169. Hotary K.B., and Robinson K.R. Evidence of a role for endogenous electrical fields in chick embryo development. Development 114 (1992) 985-996
170. Sisken B.F. Electrical-stimulation of nerves and their regeneration. Bioelectrochem Bioener 29 (1992) 121-126
171. Sisken B.F., Walker J., and Orgel M. Prospects on clinical-applications of electrical-stimulation for nerve regeneration. J Cell Biochem 51 (1993) 404-409
172. Sharma K.K., and Niazi I.A. Restoration of limb regeneration ability in frog tadpoles by electrical stimulation. Indian J Exp Biol 28 (1990) 733-738
173. Smith S.D. Induction of partial limb regeneration in Rana pipiens by galvanic stimulation. Anat Rec 158 (1967) 89
174. Borgens R.B., Vanable Jr. J.W., and Jaffe L.F. Bioelectricity and regeneration. I. Initiation of frog limb regeneration by minute currents. J Exp Zool 200 (1977) 403-416
175. Smith S.D. The role of electrode position in the electrical induction of limb regeneration in subadult rats. Bioelectrochem Bioener 8 (1981) 661-670
176. Sisken B.F., and Fowler I. Induction of limb regeneration in the chick-embryo. Anat Rec 199 (1981) A238-A239
177. Becker R.O. Stimulation of partial limb regeneration in rats. Nature 235 (1972) 109-111
178. Sisken B.F., Fowler I., and Romm S. Response of amputated rat limbs to fetal nerve tissue implants and direct current. J Orthop Res 2 (1984) 177-189
179. +-ATPase is a dominant negative mutant and is sequestered in endoplasmic reticulum derived structures. Biochem Cell Biol 78 (2000) 51-58
180. Reshkin S.J., Bellizzi A., Albarani V., Guerra L., Tommasino M., Paradiso A., et al. Phosphoinositide 3-kinase is involved in the tumor-specific activation of human breast cancer cell Na(+)/H(+) exchange, motility, and invasion induced by serum deprivation. J Biol Chem 275 (2000) 5361-5369
181. Fukumoto T., Kema I.P., and Levin M. Serotonin signaling is a very early step in patterning of the left-right axis in chick and frog embryos. Curr Biol 15 (2005) 794-803
182. Denker S.P., and Barber D.L. Cell migration requires both ion translocation and cytoskeletal anchoring by the Na-H exchanger NHE1. J Cell Biol 159 (2002) 1087-1096
183. Denker S.P., and Barber D.L. Ion transport proteins anchor and regulate the cytoskeleton. Curr Opin Cell Biol 14 (2002) 214-220
184. Jaffe L.F. Localization in the developing Fucus egg and the general role of localizing currents. Adv Morphog 7 (1968) 295-328
185. Kalmijn A.J. Electric and magnetic field detection in elasmobranch fishes. Science 218 (1982) 916-918
186. Kalmijn A.J. The electric sense of sharks and rays. J Exp Biol 55 (1971) 371-383
187. Gruler H., and Nuccitelli R. Neural crest cell galvanotaxis-new data and a novel-approach to the analysis of both galvanotaxis and chemotaxis. Cell Motil Cytoskel 19 (1991) 121-133
188. Sasaki M., Gonzalez-Zulueta M., Huang H., Herring W.J., Ahn S., Ginty D.D., et al. Dynamic regulation of neuronal NO synthase transcription by calcium influx through a CREB family transcription factor-dependent mechanism. Proc Natl Acad Sci USA 97 (2000) 8617-8622
189. Malhi H., Irani A.N., Rajvanshi P., Suadicani S.O., Spray D.C., McDonald T.V., et al. KATP channels regulate mitogenically induced proliferation in primary rat hepatocytes and human liver cell lines. Implications for liver growth control and potential therapeutic targeting. J Biol Chem 275 (2000) 26050-26057
190. Levin M., Buznikov G.A., and Lauder J.M. Of minds and embryos: left-right asymmetry and the serotonergic controls of pre-neural morphogenesis. Dev Neurosci 28 (2006) 171-185
191. Arcangeli A., and Becchetti A. Complex functional interaction between integrin receptors and ion channels. Trends Cell Biol 16 (2006) 631-639
192. Cherubini A., Hofmann G., Pillozzi S., Guasti L., Crociani O., Cilia E., et al. Human ether-a-go-go-related gene 1 channels are physically linked to beta1 integrins and modulate adhesion-dependent signaling. Mol Biol Cell 16 (2005) 2972-2983
193. + channels. Proc Natl Acad Sci USA 103 (2006) 2886-2891
194. Mazzanti M., Bustamante J.O., and Oberleithner H. Electrical dimension of the nuclear envelope. Physiol Rev 81 (2001) 1-19
195. + loss. Mol Cell Biol 26 (2006) 1038-1050
196. Yang S.J., Liang H.L., Ning G., and Wong-Riley M.T. Ultrastructural study of depolarization-induced translocation of NRF-2 transcription factor in cultured rat visual cortical neurons. Eur J Neurosci 19 (2004) 1153-1162
197. Murata Y., Iwasaki H., Sasaki M., Inaba K., and Okamura Y. Phosphoinositide phosphatase activity coupled to an intrinsic voltage sensor. Nature 435 (2005) 1239-1243
198. Li L., Liu F., Salmonsen R.A., Turner T.K., Litofsky N.S., Di Cristofano A., et al. PTEN in neural precursor cells: regulation of migration, apoptosis, and proliferation. Mol Cell Neurosci 20 (2002) 21-29
199. Zhang W., and Kone B.C. NF-kappaB inhibits transcription of the H(+)-K(+)-ATPase alpha(2)-subunit gene: role of histone deacetylases. Am J Physiol Renal Physiol 283 (2002) F904-F911
200. Jouhou H., Yamamoto K., Homma A., Hara M., Kaneko A., and Yamada M. Depolarization of isolated horizontal cells of fish acidifies their immediate surrounding by activating V-ATPase. J Physiol 585 (2007) 401-412
201. + channel components are involved in early left-right patterning in Xenopus laevis embryos. Cell Physiol Biochem 21 (2008) 357-372
202. Aw S., Adams D.S., Qiu D., and Levin M. H,K-ATPase protein localization and Kir4. 1 function reveal concordance of three axes during early determination of left-right asymmetry. Mech Dev 125 (2008) 353-372
203. Shimeld S.M., and Levin M. Evidence for the regulation of left-right asymmetry in Ciona intestinalis by ion flux. Dev Dyn 235 (2006) 1543-1553
204. Gillespie J.I. The distribution of small ions during the early development of Xenopus laevis and Ambystoma mexicanum embryos. J Physiol 344 (1983) 359-377
205. Fang K.S., Ionides E., Oster G., Nuccitelli R., and Isseroff R.R. Epidermal growth factor receptor relocalization and kinase activity are necessary for directional migration of keratinocytes in DC electric fields. J Cell Sci 112 (1999) 1967-1978
206. Poo M.M., and Robinson K.R. Electrophoresis of concanavalin-a receptors along embryonic muscle-cell membrane. Nature 265 (1977) 602-605
207. Hotary K.B., and Robinson K.R. Endogenous electrical currents and the resultant voltage gradients in the chick embryo. Dev Biol 140 (1990) 149-160
208. Borgens R.B., and Shi R. Uncoupling histogenesis from morphogenesis in the vertebrate embryo by collapse of the transneural tube potential. Dev Dyn 203 (1995) 456-467
209. Esser A.T., Smith K.C., Weaver J.C., and Levin M. Mathematical model of morphogen electrophoresis through gap junctions. Dev Dyn 235 (2006) 2144-2159
210. Burr H.S. Changes in the field properties of mice with transplanted tumors. Yale J Biol Med 13 (1941) 783-788
211. Kauffman S.A. The origins of order: self-organization and selection in evolution (1993), Oxford University Press, New York pp. xviii, 709 p
212. Martens J.R., O'Connell K., and Tamkun M. Targeting of ion channels to membrane microdomains: localization of KV channels to lipid rafts. Trends Pharmacol Sci 25 (2004) 16-21
213. Davies A., Douglas L., Hendrich J., Wratten J., Tran Van Minh A., Foucault I., et al. The calcium channel alpha2delta-2 subunit partitions with CaV2.1 into lipid rafts in cerebellum: implications for localization and function. J Neurosci 26 (2006) 8748-8757
214. Wallace R. Neural membrane microdomains as computational systems: toward molecular modeling in the study of neural disease. Biosystems 87 (2007) 20-30
215. Kline D., Robinson K.R., and Nuccitelli R. Ion currents and membrane domains in the cleaving Xenopus egg. J Cell Biol 97 (1983) 1753-1761
216. Perona R., and Serrano R. Increased pH and tumorigenicity of fibroblasts expressing a yeast proton pump. Nature 334 (1988) 438-440
217. Megason S.G., and Fraser S.E. Imaging in systems biology. Cell 130 (2007) 784-795
218. Adams D.S., and Levin M. In: Whitman M., and Sater A.K. (Eds). Analysis of growth factor signaling in embryos (2006), Taylor and Francis Books pp. 177-262
219. Smith P.J.S., Sanger R.S., and Messerli M.A. In: Michael A.C. (Ed). Methods and new frontiers in neuroscience (2007), CRC Press pp. 373-405
220. Reid B., Nuccitelli R., and Zhao M. Non-invasive measurement of bioelectric currents with a vibrating probe. Nature Protoc 2 (2007) 661-669
221. Moschou E.A., and Chaniotakis N.A. Ion-partitioning membrane-based electrochemical sensors. Anal Chem 72 (2000) 1835-1842
222. Steinberg B.E., Touret N., Vargas-Caballero M., and Grinstein S. In situ measurement of the electrical potential across the phagosomal membrane using FRET and its contribution to the proton-motive force. Proc Natl Acad Sci USA 104 (2007) 9523-9528
223. Yun Z., Zhengtao D., Jiachang Y., Fangqiong T., and Qun W. Using cadmium telluride quantum dots as a proton flux sensor and applying to detect H9 avian influenza virus. Anal Biochem 364 (2007) 122-127
224. Wolff C., Fuks B., and Chatelain P. Comparative study of membrane potential-sensitive fluorescent probes and their use in ion channel screening assays. J Biomol Screen 8 (2003) 533-543
225. Tyner K.M., Kopelman R., and Philbert M.A. "Nanosized voltmeter" enables cellular-wide electric field mapping. Biophys J 93 (2007) 1163-1174
226. Yu K., Ruan D.Y., and Ge S.Y. Three electrophysiological phenotypes of cultured human umbilical vein endothelial cells. Gen Physiol Biophys 21 (2002) 315-326
227. Adams D.S., and Levin M. Inverse drug screens: a rapid and inexpensive method for implicating molecular targets. Genesis 44 (2006) 530-540
228. Levin M. Is the early left-right axis like a plant, a kidney, or a neuron? The integration of physiological signals in embryonic asymmetry. Birth Defects Res C Embryo Today 78 (2006) 191-223
229. Adams D.S. A new tool for tissue engineers: ions as regulators of morphogenesis during development and regeneration. Tissue Eng 14 (2008) 1461-1468
230. Fischbarg J., and Diecke F.P. A mathematical model of electrolyte and fluid transport across corneal endothelium. J Membr Biol 203 (2005) 41-56
231. Pandiella A., Magni M., Lovisolo D., and Meldolesi J. The effect of epidermal growth factor on membrane potential. Rapid hyperpolarization followed by persistent fluctuations. J Biol Chem 264 (1989) 12914-12921
232. Lang F., Friedrich F., Kahn E., Woll E., Hammerer M., Waldegger S., et al. Bradykinin-induced oscillations of cell membrane potential in cells expressing the Ha-ras oncogene. J Biol Chem 266 (1991) 4938-4942
233. Hulser D.F., and Lauterwasser U. Membrane potential oscillations in homokaryons. An endogenous signal for detecting intercellular communication. Exp Cell Res 139 (1982) 63-70
234. + channel activity provide evidence for inherent metabolic oscillations in pancreatic beta-cells. Biochem Biophys Res Commun 205 (1994) 880-885
235. 2+ oscillations in pancreatic beta-cells. Arch Biochem Biophys 300 (1993) 372-377
236. + can synchronize bursting oscillations in a model islet of Langerhans. Biophys J 65 (1993) 597-607
237. + concentration in Dictyostelium discoideum. EMBO J 4 (1985) 39-43
238. Giulian D., and Diacumakos E.G. The electrophysiological mapping of compartments within a mammalian cell. J Cell Biol 72 (1977) 86-103
239. Liebau S., Propper C., Bockers T., Lehmann-Horn F., Storch A., Grissmer S., et al. Selective blockage of Kv1.3 and Kv3. 1 channels increases neural progenitor cell proliferation. J Neurochem 99 (2006) 426-437
240. Banghart M., Borges K., Isacoff E., Trauner D., and Kramer R.H. Light-activated ion channels for remote control of neuronal firing. Nat Neurosci 7 (2004) 1381-1386
241. Chambers J.J., Banghart M.R., Trauner D., and Kramer R.H. Light-induced depolarization of neurons using a modified Shaker K(+) channel and a molecular photoswitch. J Neurophysiol 96 (2006) 2792-2796
242. Gradinaru V., Thompson K.R., and Deisseroth K. eNpHR: a Natronomonas halorhodopsin enhanced for optogenetic applications. Brain Cell Biol 36 (2008) 129-139
243. Miesenbock G., De Angelis D.A., and Rothman J.E. Visualizing secretion and synaptic transmission with pH-sensitive green fluorescent proteins. Nature 394 (1998) 192-195
244. Tsutsui H., Karasawa S., Okamura Y., and Miyawaki A. Improving membrane voltage measurements using FRET with new fluorescent proteins. Nat Methods 5 (2008) 683-685
245. Zhao S., Cunha C., Zhang F., Liu Q., Gloss B., Deisseroth K., et al. Improved expression of halorhodopsin for light-induced silencing of neuronal activity. Brain Cell Biol 36 (2008) 141-154
246. Zhang F., Wang L.P., Brauner M., Liewald J.F., Kay K., Watzke N., et al. Multimodal fast optical interrogation of neural circuitry. Nature 446 (2007) 633-639
247. Wang H., Peca J., Matsuzaki M., Matsuzaki K., Noguchi J., Qiu L., et al. High-speed mapping of synaptic connectivity using photostimulation in Channelrhodopsin-2 transgenic mice. Proc Natl Acad Sci USA 104 (2007) 8143-8148
248. Stern C. Experimental reversal of polarity in chick embryo epiblast sheets in vitro. Exp Cell Res 140 (1982) 468-471
249. Woodruff R.I. Calmodulin transit via gap junctions is reduced in the absence of an electric field. J Insect Physiol 51 (2005) 843-852
250. Kurtz I., and Schrank A.R. Bioelectrical properties of intact and regenerating earthworms Eisenia foetida. Physiol Zool 28 (1955) 322-330
251. Uzman J.A., Patil S., Uzgare A.R., and Sater A.K. The role of intracellular alkalinization in the establishment of anterior neural fate in Xenopus. Dev Biol 193 (1998) 10-20