Controlling Cell Behavior Electrically: Current Views and Future Potential

McCaig, Colin; Rajnicek, Ann M.; Song, Bing; Zhao, Min

doi:10.1152/physrev.00020.2004

Cited by 896 publications

(950 citation statements)

References 209 publications

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“…Thus, it is conceivable that the external application of a microcurrent could normalize the endogenous electrical gradient, either by influencing the existing current gradient or by triggering protein activation to induce favourable cellular responses 30. Initial evidence showing that electrical signals can modulate kinase activity was reported in a paper published by Zhao and colleagues in Nature 31.…”

Section: Discussionmentioning

confidence: 99%

Bioelectrical signals improve cardiac function and modify gene expression of extracellular matrix components

et al. 2017

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AimsBeyond the influence of stimulating devices on cardiac excitation, their use in treating patients with heart failure has positive effects on the myocardium at the molecular level. Electrical signals can induce a wide spectrum of effects in living tissue. Therefore, we sought to determine whether applying electrical microcurrent directly to failing hearts leads to functional improvement.Methods and resultsSixteen male spontaneously hypertensive rats (SHRs) with heart failure underwent application of a patch electrode to the left ventricular epicardium and placement of a subcutaneous counter electrode. The electrode delivered a 0.35 μA microcurrent to nine of the SHRs for 45 ± 3 days; the other seven SHRs were used as controls. At baseline and before the SHRs were humanely put to death, we measured the left ventricular ejection fraction (LVEF) and the thickness of the LV posterior wall during systole and diastole (LVPWs/d). We used quantitative PCR to determine extracellular matrix parameters [collagen I–III, matrix metalloproteinase (MMP)‐2, MMP‐9, tissue inhibitor of metalloproteinases 3 (TIMP3), TIMP4, connexins (Cxs) 40/43/45, transforming growth factor (TGF)‐β, and interleukin (IL)‐6].Among SHRs undergoing microcurrent application, LVEF normalized (mean decrease, 22.8%; P = 0.009), and LVPWs decreased (mean, 35.3%; P = 0.001). Compared with the control group, the SHRs receiving microcurrent exhibited a mean decrease in the gene expression of collagen I (10.6%, P = 0.003), TIMP3 (18.5%, P = 0.005), Cx43 (14.3%, P = 0.003), Cx45 (12.7%, P = 0.020), TGF‐β (13.0%, P = 0.005), and IL‐6 (53.7%, P = 0.000). Microcurrent application induced no changes in the expression of collagen III, MMP‐2, MMP‐9, TIMP4, or Cx40.ConclusionsApplying microcurrent to the LV epicardium of SHRs leads to statistically significant functional improvement and alterations in the levels of inflammatory and extracellular matrix components.

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Section: Discussionmentioning

confidence: 99%

Bioelectrical signals improve cardiac function and modify gene expression of extracellular matrix components

et al. 2017

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“…It is well documented that endogenous electric fields play a role in regeneration, and it has been shown that applied electric fields are able to enhance regeneration and repair in vertebrates (Borgens et al, 1977(Borgens et al, , 1981Kerns and Lucchinetti, 1992;McCaig et al, 2005). have recently demonstrated a molecular link between electric currents and tail regeneration in Xenopus.…”

Section: Electric Currents and Regenerationmentioning

confidence: 99%

Beyond early development: Xenopus as an emerging model for the study of regenerative mechanisms

Beck

Belmonte

Christen

2009

Developmental Dynamics

146

139

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While Xenopus is a well-known model system for early vertebrate development, in recent years, it has also emerged as a leading model for regeneration research. As an anuran amphibian, Xenopus laevis can regenerate the larval tail and limb by means of the formation of a proliferating blastema, the lens of the eye by transdifferentiation of nearby tissues, and also exhibits a partial regeneration of the postmetamorphic froglet forelimb. With the availability of inducible transgenic techniques for Xenopus, recent experiments are beginning to address the functional role of genes in the process of regeneration. The use of soluble inhibitors has also been very successful in this model. Using the more traditional advantages of Xenopus, others are providing important lineage data on the origin of the cells that make up the tissues of the regenerate. Finally, transcriptome analyses of regenerating tissues seek to identify the genes and cellular processes that enable successful regeneration.

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“…Thus, functional GJC is dependant on the existence of compatible hemichannels on the cells' surfaces, the permeability of the hemichannels to the substance, and the open status of the gap junction. Regulated GJC paths serve to establish patterns of iso-potential and/or iso-pH cell fields (Sherman and Rinzel, 1991;Fitzharris and Baltz, 2006;Rocheleau et al, 2006); this epigenetic "prepattern" overlaid upon the embryonic morphology, working in concert with the molecular fields defined by gene expression domains, is an important control element in embryonic patterning (Levin, 2003a;Nuccitelli, 2003;McCaig et al, 2005). This extremely versatile system for communication allows for rapid synchronization among cells in a tissue and the passage of signals, both of which can be regulated at many levels.…”

Section: Behavior Is Dependent Upon Gap Junction (Gj) -Mediated Signalsmentioning

confidence: 99%

Mathematical model of morphogen electrophoresis through gap junctions

Esser

Smith

Weaver

et al. 2006

Developmental Dynamics

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Gap junctional communication is important for embryonic morphogenesis. However, the factors regulating the spatial properties of small molecule signal flows through gap junctions remain poorly understood. Recent data on gap junctions, ion transporters, and serotonin during left-right patterning suggest a specific model: the net unidirectional transfer of small molecules through long-range gap junctional paths driven by an electrophoretic mechanism. However, this concept has only been discussed qualitatively, and it is not known whether such a mechanism can actually establish a gradient within physiological constraints. We review the existing functional data and develop a mathematical model of the flow of serotonin through the early Xenopus embryo under an electrophoretic force generated by ion pumps. Through computer simulation of this process using realistic parameters, we explored quantitatively the dynamics of morphogen movement through gap junctions, confirming the plausibility of the proposed electrophoretic mechanism, which generates a considerable gradient in the available time frame. The model made several testable predictions and revealed properties of robustness, cellular gradients of serotonin, and the dependence of the gradient on several developmental constants. This work quantitatively supports the plausibility of electrophoretic control of morphogen movement through gap junctions during early left-right patterning. This conceptual framework for modeling gap junctional signaling-an epigenetic patterning mechanism of wide relevance in biological regulation-suggests numerous experimental approaches in other patterning systems.

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Controlling Cell Behavior Electrically: Current Views and Future Potential

Cited by 896 publications

References 209 publications

Bioelectrical signals improve cardiac function and modify gene expression of extracellular matrix components

Bioelectrical signals improve cardiac function and modify gene expression of extracellular matrix components

Beyond early development: Xenopus as an emerging model for the study of regenerative mechanisms

Mathematical model of morphogen electrophoresis through gap junctions

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