Electric fields and wound healing

Jaffe, Lionel F.; Vanable, Joseph W.

doi:10.1016/0738-081x(84)90025-7

Cited by 130 publications

(69 citation statements)

References 25 publications

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“…Electrical potentials over skin wounds are initially positive but become negative after the fourth day of healing and remain negative until healing is completed (64). The source of putative skin battery driving such currents resides within the living epidermal layer made by KCs (50,65) and may involve the keratinocyte ACh axis.…”

Section: Discussionmentioning

confidence: 99%

The Ras/Raf-1/MEK1/ERK Signaling Pathway Coupled to Integrin Expression Mediates Cholinergic Regulation of Keratinocyte Directional Migration

Chernyavsky

Arredondo

Karlsson

et al. 2005

Journal of Biological Chemistry

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The physiologic mechanisms that determine directionality of lateral migration are a subject of intense research. Galvanotropism in a direct current (DC) electric field represents a natural model of cell re-orientation toward the direction of future migration. Keratinocyte migration is regulated through both the nicotinic and muscarinic classes of acetylcholine (ACh) receptors. We sought to identify the signaling pathway mediating the cholinergic regulation of chemotaxis and galvanotropism. The pharmacologic and molecular modifiers of the Ras/Raf-1/MEK1/ERK signaling pathway altered both chemotaxis toward choline and galvanotropism toward the cathode in a similar way, indicating that the same signaling steps were involved. The galvanotropism was abrogated due to inhibition of ACh production by hemicholinium-3 and restored by exogenously added carbachol. The concentration gradients of ACh and choline toward the cathode in a DC field were established by highperformance liquid chromatographic measurements. This suggested that keratinocyte galvanotaxis is, in effect, chemotaxis toward the concentration gradient of ACh, which it creates in a DC field due to its highly positive charge. A time-course immunofluorescence study of the membrane redistribution of ACh receptors in keratinocytes exposed to a DC field revealed rapid relocation to and clustering at the leading edge of ␣7 nicotinic and M 1 muscarinic receptors. Their inactivation with selective antagonists or small interfering RNAs inhibited galvanotropism, which could be prevented by transfecting the cells with constitutively active MEK1. The end-point effect of the cooperative signaling downstream from ␣7 and M 1 through the MEK1/ERK was an up-regulated expression of ␣ 2 and ␣ 3 integrins, as judged from the results of real-time PCR and quantitative immunoblotting. Thus, ␣7 works together with M 1 to orient a keratinocyte toward direction of its future migration. Both ␣7 and M 1 apparently engage the Ras/Raf/MEK/ERK pathway to up-regulate expression of the "sedentary" integrins required for stabilization of the lamellipodium at the keratinocyte leading edge. Human epidermal keratinocytes (KCs)2 can synthesize and secrete acetylcholine (ACh) and use it as a local hormone for an autocrine and paracrine control of their vital functions, including motility (1). ACh and its congeners are chemotactic for KCs, neurons, and other cell types (2-8). To characterize the physiologic control of keratinocyte migration, we developed an in vitro model of skin epithelialization, termed the agarose gel keratinocyte outgrowth system (AGKOS) (9). Using AGKOS, we have demonstrated that activation of the keratinocyte nicotinic ACh receptors (nAChRs) comprised by ␣7 subunits exhibit reciprocal effects on cell motility by stimulating directional (chemotaxis) and inhibiting random (chemokinesis) migration and that ACh-gated ion channels containing ␣3 subunit stimulate chemokinesis of KCs (8).More recently, ␣7 nAChR has been shown to mediate chemotaxis of vascular smooth muscle cells to...

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Section: Discussionmentioning

confidence: 99%

The Ras/Raf-1/MEK1/ERK Signaling Pathway Coupled to Integrin Expression Mediates Cholinergic Regulation of Keratinocyte Directional Migration

Chernyavsky

Arredondo

Karlsson

et al. 2005

Journal of Biological Chemistry

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“…DC electric fields (EFs) exist where cell migrations occur: in embryonic development and during wound healing of skin and cornea (Jaffe and Vanable, 1984;Chiang et al, 1992;Shi and Borgens, 1995;Robinson and Messerli, 1996). EFs equivalent to the field strength in vivo induce directed movement of cultured cells.…”

Section: Introductionmentioning

confidence: 99%

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

Zhao

Dick

Forrester

et al. 1999

MBoC

160

127

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Wounding corneal epithelium establishes a laterally oriented, DC electric field (EF). Corneal epithelial cells (CECs) cultured in similar physiological EFs migrate cathodally, but this requires serum growth factors. Migration depends also on the substrate. On fibronectin (FN) or laminin (LAM) substrates in EF, cells migrated faster and more directly cathodally. This also was serum dependent. Epidermal growth factor (EGF) restored cathodal-directed migration in serum-free medium. Therefore, the hypothesis that EGF is a serum constituent underlying both field-directed migration and enhanced migration on ECM molecules was tested. We used immunofluorescence, flow cytometry, and confocal microscopy and report that 1) EF exposure up-regulated the EGF receptor (EGFR); so also did growing cells on substrates of FN or LAM; and 2) EGFRs and actin accumulated in the cathodal-directed half of CECs, within 10 min in EF. The cathodal asymmetry of EGFR and actin staining was correlated, being most marked at the cell-substrate interface and showing similar patterns of asymmetry at various levels through a cell. At the cell-substrate interface, EGFRs and actin frequently colocalized as interdigitated, punctate spots resembling tank tracks. Cathodal accumulation of EGFR and actin did not occur in the absence of serum but were restored by adding ligand to serum-free medium. Inhibition of MAPK, one second messenger engaged by EGF, significantly reduced EF-directed cell migration. Transforming growth factor ␤ and fibroblast growth factor also restored cathodal-directed cell migration in serum-free medium. However, longer EF exposure was needed to show clear asymmetric distribution of the receptors for transforming growth factor ␤ and fibroblast growth factor. We propose that up-regulated expression and redistribution of EGFRs underlie cathodaldirected migration of CECs and directed migration induced by EF on FN and LAM.

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“…Reports on the efficacy of cryotherapy [5,6,8] and TENS [2] are generally disappointing, while the use of CPM to control pain is controversial [11]. While several investigators have reported a favourable effect of MCT on pain control and tissue healing through the modification and recruitment of cell membrane ATP (adenosine triphosphate), this occurred mostly under conditions of chronic pain [3,7]. If MCT proves to be a reliable and effective method to control pain postoperatively while avoiding the side effects associated with pharmacologically based methods, a new approach for postoperative pain management would be available to the orthopaedic surgeon.…”

Section: Discussionmentioning

confidence: 99%

Microcurrent skin patches for postoperative pain control in total knee arthroplasty: a pilot study

El-Husseini

El-Kawy

Shalaby

et al. 2006

International Orthopaedics (SICOT)

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Pain control following painful orthopaedic procedures such as total knee arthroplasty (TKA) is an ongoing challenge, as current pain management techniques often result in under-medication and/or complications. In a study designed to test the effect of the micro-current skin patch (MCT) on pain relief in patients following TKA, we followed 24 patients, randomly divided into two groups, one group receiving MCT plus tramadol hydrochloride (tramadol) for pain relief and a control group receiving only tramadol,

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Electric fields and wound healing

Cited by 130 publications

References 25 publications

The Ras/Raf-1/MEK1/ERK Signaling Pathway Coupled to Integrin Expression Mediates Cholinergic Regulation of Keratinocyte Directional Migration

The Ras/Raf-1/MEK1/ERK Signaling Pathway Coupled to Integrin Expression Mediates Cholinergic Regulation of Keratinocyte Directional Migration

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

Microcurrent skin patches for postoperative pain control in total knee arthroplasty: a pilot study

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