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Altered β-Cell Calcium Dynamics via Electric Field Exposure

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Abstract

Electric field stimulation has long been investigated with results supporting its therapeutic potential; however, its effects on insulin secreting cells has yet to be fully elucidated. Herein we explored the effects of physiological direct current (DC) electric field stimulation on the intracellular calcium dynamics of mouse derived βTC-6 insulinoma cells. This electrical stimulation resulted in an elevation in intracellular calcium along with a rise in calcium spiking activity. Further investigation indicated that the rise in intracellular calcium was mediated by an influx of calcium via L-type voltage gated calcium channels. Additionally, the effects of the electric field stimulation were able to induce insulin secretion in the absence of glucose stimulation. Given these results, DC electric field stimulation could be used as a non-invasive tool to modulate intracellular calcium dynamics and insulin secretion of β-cells for therapeutic application.

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References

  1. Allen, G., A. Mogilner, and J. Theriot. Electrophoresis of cellular membrane components creates the directional cue guiding keratocyte galvanotaxis. Curr. Biol. 23:560–568, 2013.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Balint, R., N. Cassidy, and S. Cartmell. Electrical stimulation: a novel tool for tissue engineering. Tissue Eng. B 19:48–57, 2013.

    CAS  Google Scholar 

  3. Bardy, G., A. Virsolvy, J. Quignard, M. Ravier, G. Bertrand, S. Dalle, G. Cros, R. Magous, S. Richard, and C. Oiry. Quercetin induces insulin secretion by direct activation of l-type calcium channels in pancreatic beta cells. Br. J. Pharmacol. 169:1102–1113, 2013.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Bedlack, R., M. Wei, and L. Loew. Localized membrane depolarizations and localized calcium influx during electric field-guided neurite growth. Neuron 9:393–403, 1992.

    CAS  PubMed  Google Scholar 

  5. Beebe, S., P. Blackmore, J. White, R. Joshi, and K. Schoenbach. Nanosecond pulsed electric fields modulate cell function through intracellular signal transduction mechanisms. Physiol. Meas. 25(4):1077–1093, 2004.

    PubMed  Google Scholar 

  6. Berdan, C., K. Erion, N. Burritt, B. Corkey, and J. Deeney. Inhibition of monoacylglycerol lipase activity decreases glucose-stimulated insulin secretion in INS-1 (832/13) cells and rat islets. PLoS ONE 11:e0149008, 2016.

    PubMed  PubMed Central  Google Scholar 

  7. Bertram, R., A. Sherman, and L. S. Satin. Electrical bursting, calcium oscillations, and synchronization of pancreatic islets. In: The Islets of Langerhans. Advances in Experimental Medicine and Biology, Vol. 654, edited by M. Islam. Dordrecht: Springer, 2010.

    Google Scholar 

  8. Borys, P. On the biophysics of cathodal galvanotaxis in rat prostate cancer cells: Poisson–Nernst–Planck equation approach. Eur. Biophys. J. 41:527–534, 2012.

    PubMed  PubMed Central  Google Scholar 

  9. Brüning, D., K. Reckers, P. Drain, and I. Rustenbeck. Glucose but not KCl diminishes submembrane granule turnover in mouse beta-cells. J. Mol. Endocrinol. 59:311–324, 2017.

    PubMed  Google Scholar 

  10. Budde, T., S. Meuth, and H. Pape. Calcium-dependent inactivation of neuronal calcium channels. Nat. Rev. Neurosci. 3:873–883, 2002.

    CAS  PubMed  Google Scholar 

  11. Chen, B., J. Tjahja, S. Malla, C. Liebman, and M. Cho. Astrocyte viability and functionality in spatially confined microcavitation zone. ACS Appl. Mater. Interfaces. 11:4889–4899, 2019.

    CAS  PubMed  Google Scholar 

  12. Cho, M. A review of electrocoupling mechanisms mediating facilitated wound healing. IEEE Trans. Plasma Sci. 30:1504–1515, 2002.

    CAS  Google Scholar 

  13. Cho, M., H. Thatte, R. Lee, and D. Golan. Induced redistribution of cell surface receptors by alternating current electric fields. FASEB J. 8:771–776, 1994.

    CAS  PubMed  Google Scholar 

  14. Cho, M. R., H. S. Thatte, M. T. Silvia, and D. E. Golan. Transmembrane calcium influx induced by ac electric fields. FASEB J. 13:677–683, 1999.

    CAS  PubMed  Google Scholar 

  15. Cho, M., et al. Membrane dynamics of the water transport protein Aquaporin-1 in intact human red cells. Biophys. J . 76:1136–1144, 1999.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Dubé, J., et al. Human keratinocytes respond to direct current stimulation by increasing intracellular calcium: preferential response of poorly differentiated cells. J. Cell. Physiol. 227:2660–2667, 2012.

    PubMed  Google Scholar 

  17. Fridlyand, L., N. Tamarina, and L. Philipson. Bursting and calcium oscillations in pancreatic β-cells: specific pacemakers for specific mechanisms. Am. J. Physiol. 299:E517–E532, 2010.

    CAS  Google Scholar 

  18. Funk, R. Endogenous electric fields as guiding cue for cell migration. Front. Physiol. 2015. https://doi.org/10.3389/fphys.2015.00143/full.

    Article  PubMed  PubMed Central  Google Scholar 

  19. García-Montalvo, E., H. Reyes-Pérez, and L. Del Razo. Fluoride exposure impairs glucose tolerance via decreased insulin expression and oxidative stress. Toxicology 263:75–83, 2009.

    PubMed  Google Scholar 

  20. Gilon, P., H. Chae, G. Rutter, and M. Ravier. Calcium signaling in pancreatic β-cells in health and in type 2 diabetes. Cell Calcium 56:340–361, 2014.

    CAS  PubMed  Google Scholar 

  21. Henquin, J., N. Ishiyama, M. Nenquin, M. Ravier, and J. Jonas. Signals and pools underlying biphasic insulin secretion. Diabetes 51:S60–S67, 2002.

    CAS  PubMed  Google Scholar 

  22. Joshi, R., A. Nguyen, V. Sridhara, Q. Hu, R. Nuccitelli, S. Beebe, J. Kolb, and K. Schoenbach. Simulations of intracellular calcium release dynamics in response to a high-intensity, ultrashort electric pulse. Phys. Rev. E 75(4):041920, 2007.

    CAS  Google Scholar 

  23. Khatib, L., D. Golan, and M. Cho. Physiologic electrical stimulation provokes intracellular calcium increase mediated by phospholipase C activation in human osteoblasts. FASEB J. 18:1903–1905, 2004.

    CAS  PubMed  Google Scholar 

  24. Kloth, L. Electrical stimulation for wound healing: a review of evidence from in vitro studies, animal experiments, and clinical trials. Int. J. Low. Extrem. Wounds 4:23–44, 2005.

    PubMed  Google Scholar 

  25. Kwon, K., R. Nityanandam, J. New, and H. Daniell. Oral delivery of bioencapsulated exendin-4 expressed in chloroplasts lowers blood glucose level in mice and stimulates insulin secretion in beta-TC6 cells. Plant Biotechnol. J. 11:77–86, 2012.

    PubMed  PubMed Central  Google Scholar 

  26. Ladewig, T., and B. Keller. Simultaneous patch-clamp recording and calcium imaging in a rhythmically active neuronal network in the brainstem slice preparation from mouse. Pflüg. Arch. 440:322, 2000.

    CAS  Google Scholar 

  27. Lee, R., T. Gowrishankar, R. Basch, P. Patel, and D. Golan. Cell shape-dependent rectification of surface receptor transport in a sinusoidal electric field. Biophys. J . 64:44–57, 1993.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Matschinsky, F. Regulation of pancreatic β-cell glucokinase: from basics to therapeutics. Diabetes 51:S394–S404, 2002.

    CAS  Google Scholar 

  29. Mycielska, M., and M. Djamgoz. Cellular mechanisms of direct-current electric field effects: galvanotaxis and metastatic disease. J. Cell Sci. 117:1631–1639, 2004.

    CAS  PubMed  Google Scholar 

  30. Navarro-Tableros, V., T. Fiordelisio, A. Hernández-Cruz, and M. Hiriart. Physiological development of insulin secretion, calcium channels, and GLUT2 expression of pancreatic rat β-cells. Am. J. Physiol. 292:E1018–E1029, 2007.

    CAS  Google Scholar 

  31. NCD Risk Factor Collaboration. Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4·4 million participants. Lancet 387:1513–1530, 2016.

    Google Scholar 

  32. Page, K., and T. Reisman. Interventions to preserve beta-cell function in the management and prevention of type 2 diabetes. Curr. Diab. Rep. 13:252–260, 2013.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Pedersen, M., and A. Sherman. Newcomer insulin secretory granules as a highly calcium-sensitive pool. Proc. Natl. Acad. Sci. USA 106:7432–7436, 2009.

    CAS  PubMed  Google Scholar 

  34. Poitout, V. Minireview: secondary-cell failure in type 2 diabetes–a convergence of glucotoxicity and lipotoxicity. Endocrinology 143:339–342, 2002.

    CAS  PubMed  Google Scholar 

  35. Radman, T., Y. Su, J. An, L. Parra, and M. Bikson. Spike timing amplifies the effect of electric fields on neurons: implications for endogenous field effects. J. Neurosci. 27:3030–3036, 2007.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Robertson, R. Chronic oxidative stress as a central mechanism for glucose toxicity in pancreatic islet beta cells in diabetes. J. Biol. Chem. 279:42351–42354, 2004.

    CAS  PubMed  Google Scholar 

  37. Rosenmund, C., A. Feltz, and G. Westbrook. Calcium-dependent inactivation of synaptic NMDA receptors in hippocampal neurons. J. Neurophysiol. 73:427–430, 1995.

    CAS  PubMed  Google Scholar 

  38. Schoenbach, K., et al. Ultrashort electrical pulses open a new gateway into biological cells. Proc. IEEE 92:1122–1137, 2004.

    CAS  Google Scholar 

  39. Seino, S. Cell signalling in insulin secretion: the molecular targets of ATP, cAMP and sulfonylurea. Diabetologia 55:2096–2108, 2012.

    CAS  PubMed  Google Scholar 

  40. Seino, S., T. Shibasaki, and K. Minami. Dynamics of insulin secretion and the clinical implications for obesity and diabetes. J. Clin. Investig. 121:2118–2125, 2011.

    CAS  PubMed  Google Scholar 

  41. Tank, D., W. Fredericks, L. Barak, and W. Webb. Electric field-induced redistribution and postfield relaxation of low density lipoprotein receptors on cultured human fibroblasts. J Cell Biol. 101(1):148–157, 1985.

    CAS  PubMed  Google Scholar 

  42. Vernier, P., Y. Sun, L. Marcu, S. Salemi, C. Craft, and M. Gundersen. Calcium bursts induced by nanosecond electric pulses. Biochem. Biophys. Res. Commun. 310(2):286–295, 2003.

    CAS  PubMed  Google Scholar 

  43. Zaiontz, C., The data analysis for this paper was generated using the Real Statistics Resource Pack software (Release 6.2). Copyright, 2013–2019.

  44. Zhang, J., R. Ren, X. Luo, P. Fan, X. Liu, S. Liang, L. Ma, P. Yu, and H. Bai. A small physiological electric field mediated responses of extravillous trophoblasts derived from HTR8/SVneo cells: involvement of activation of focal adhesion kinase signaling. PLoS ONE 2014. https://doi.org/10.1371/journal.pone.0092252.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This work was supported in part by the generous donations from Drs. Alfred and Janet Potvin.

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Correspondence to Michael Cho.

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Associate Editor Debra T. Auguste oversaw the review of this article.

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Liebman, C., Vu, TM., Phillips, A. et al. Altered β-Cell Calcium Dynamics via Electric Field Exposure. Ann Biomed Eng 49, 106–114 (2021). https://doi.org/10.1007/s10439-020-02517-w

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  • DOI: https://doi.org/10.1007/s10439-020-02517-w

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