Cited by 468Ion channel regulation and functionIon Transport and Channel RegulationConnexins and lens biology

Bioelectric controls of cell proliferation: Ion channels, membrane voltage and the cell cycle

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Blackiston, Douglas J., McLaughlin, Kelly A., Levin, Michael·2009·Cell Cycle

Abstract

All cells possess long-term, steady-state voltage gradients across the plasma membrane. These transmembrane potentials arise from the combined activity of numerous ion channels, pumps and gap junction complexes. Increasing data from molecular physiology now reveal that the role of changes in membrane voltage controls, and is in turn controlled by, progression through the cell cycle. We review recent functional data on the regulation of mitosis by bioelectric signals, and the function of membrane voltage and specific potassium, sodium and chloride ion channels in the proliferation of embryonic, somatic and neoplastic cells. Its unique properties place this powerful, well-conserved, but still poorly-understood signaling system at the center of the coordinated cellular interactions required for complex pattern formation. Moreover, disregulation of ion channel expression and function is increasingly observed to be not only a useful marker but likely a functional element in oncogenesis. New advances in genomics and the development of in vivo biophysical techniques suggest exciting opportunities for molecular medicine, bioengineering and regenerative approaches to human health.

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  • Changes in Vm control critical cell functions including proliferation, migration, and differentiation.

    “Since then, changes in Vm, representing the long-term, slowly changing bioelectric gradient in non-excitable cells (Lobikin et al., 2012), have been shown to control critical cell functions including proliferation, migration, and differentiation (Binggeli and Weinstein, 1986; Schwab et al., 2007; Blackiston et al., 2009; Sundelacruz et al., 2009).”

    From Membrane potential and cancer progression (2013) · cites this paper as Blackiston et al., 2009

    The sections on Vmem and cell proliferation and on regenerative medicine describe voltage-dependent control of proliferation. The Vmem and cell proliferation section also reports that changing membrane potential can alter differentiation in human mesenchymal stem cells. Our copy does not establish that changes in Vmem control migration; its mention of cell migration occurs in a reference title about an ion exchanger. (LLM, conf=0.86)

    Experimental — accuracy not yet measured
  • The Vm fluctuates during cell cycle progression, and follows a multi-step and rhythmic pattern.

    “An additional layer of complexity in this model is that the Vm fluctuates during cell cycle progression, and follows a multi-step and rhythmic pattern (Wonderlin and Strobl, 1996; Blackiston et al., 2009) (Figure 2).”

    From Membrane potential and cancer progression (2013) · cites this paper as Blackiston et al., 2009

  • Modulation of chloride, sodium, potassium, and calcium channel activity has been found to contribute to the relatively depolarized resting Vm in cancer cells.

    “Modulation of chloride, sodium, potassium, and calcium channel activity has also been found to contribute to the relatively depolarized resting Vm in cancer cells [71].”

    From Permeabilizing Cell Membranes with Electric Fields (2021) · cites this paper as [71]

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1 retracted

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Research works printed but not linked: 2

  1. [37]Robinson K Messerli M McCaig C Electric embryos: the embryonic epithelium as a generator of developmental information Nerve Growth and Guidance 1996 Portland Portland Press 131 141
  2. [110]Binggeli R Weinstein RC Membrane potentials and sodium channels: hypotheses for growth regulation and cancer formation based on changes in sodium channels and gap junctions J Theor Biol 1986 123 377 401 2443763

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Authors
Blackiston, D. J., McLaughlin, K. A., & Levin, M.
Affiliations
Tufts University (US)
Corresponding author
Levin, Michael
Venue
Cell Cycle
Published
2009-11
Volume
8
Issue
21
Pages
3527-3536
ISSN
  • 1538-4101 (ISSN-L)
  • 1551-4005
OpenAlex
W2003046273
Cited by
468
References
175
Citations by year
2026: 17 · 2025: 28 · 2024: 39 · 2023: 28 · 2022: 38 · 2021: 33 · 2020: 33 · 2019: 36 · 2018: 28 · 2017: 31 · 2016: 28 · 2015: 28 · 2014: 32 · 2013: 25 · 2012: 21
FWCI
5.91
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Cell Cycle (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Eye Institute (EY018168, R01EY018168)
  • National Institute of General Medical Sciences (R01GM078484, GM078484, R01GM077425)
  • National Institute of Dental and Craniofacial Research (T32DE007327)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
Keywords
membrane potential, bioelectric signaling, cell proliferation, ion channels, mitosis regulation, potassium channels, sodium channels, chloride channels, gap junctions, carcinogenesis, embryonic development, neoplastic cells
MeSH terms
Animals, Cell Cycle, Humans, Ion Channels, Membrane Potentials, Neoplasms, Cell Proliferation

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