Endogenous lateral electric fields around bovine corneal lesions are necessary for and can enhance normal rates of wound healing

Iglesia, Drina D. Sta.; Vanable, Joseph W.

doi:10.1046/j.1524-475x.1998.60606.x

Cited by 70 publications

(70 citation statements)

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“…The lateral EF is driven by the transepithelial potential through the low-resistance wound pathway, creating a negative pole (cathode) at the center of the wound (Ojingwa and Isseroff, 2003). Endogenous direct current (DC) EFs of 40-200 mV mm -1 have been measured near wounds in mammalian epithelia (Barker et al, 1982;Chiang et al, 1992;McGinnis and Vanable, 1986;Sta Iglesia et al, 1996;Sta Iglesia and Vanable, 1998). Human neonatal keratinocytes do indeed sense the EF within minutes, re-form their lamellipodia facing the cathode and migrate directionally in physiological DC EFs of 100 mV mm -1 in vitro, a process known as galvanotaxis (Nishimura et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Cyclic AMP mediates keratinocyte directional migration in an electric field

Pullar

Isseroff

2005

Journal of Cell Science

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Re-epithelialization of wounded skin is necessary for wound closure and restoration of barrier function and requires directional keratinocyte migration towards the center of the wound. The electric field (EF) generated immediately upon wounding could be the earliest signal keratinocytes receive to initiate directional migration and healing. Keratinocytes express many β2-adrenergic receptors (β2-ARs), but their role in the epidermis is unknown. We have previously shown that β-AR agonists decrease keratinocyte migration in a cyclic AMP (cAMP) independent mechanism involving the activation of protein phosphatase 2A (PP2A). Here, we ask whether β2-ARs play a role in keratinocyte galvanotaxis. We report a bimodal response. When keratinocytes were exposed to higher concentrations of β-AR agonist (0.1 μM), their tracked migratory speed was inhibited, in both the presence (directional migration) and the absence (random migration) of a 100 mV mm–1 EF, as expected. At lower agonist concentrations (0.1 pM to 0.1 nM), there was no effect on migratory speed; however, all directionality was lost – essentially, cells were `blinded' to the directional cue. Preincubating the cells with β-antagonist restored directional migration, demonstrating that the `blindness' was β2-AR mediated. Incubation of keratinocytes with agents known to increase intracellular cAMP levels, such as sp-cAMP, pertussis toxin and forskolin, resulted in similar `blinding' to the EF, whereas random migration was unaffected. The inactive cAMP analog rp-cAMP had no effect on keratinocyte migration, whether directional or random. However, rp-cAMP pretreatment before β-agonist addition fully restored galvanotaxis, demonstrating the complete cAMP dependence of the attenuation of keratinocyte directional migration. This is the first report that cAMP is capable of mediating keratinocyte galvanotaxis. β-AR agonists and antagonists could be valuable tools for modulating re-epithelialization, an essential step in the wound-healing process. Thus, β-ARs regulate the two distinct components of keratinocyte directional migration differently: migration speed via a cAMP-independent mechanism and galvanotaxis by a cAMP-dependent one.

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Section: Introductionmentioning

confidence: 99%

Cyclic AMP mediates keratinocyte directional migration in an electric field

Pullar

Isseroff

2005

Journal of Cell Science

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“…We used the EFs within this range because the strength of endogenous dcEFs in animal body is known to be 50-500 mV/mm. 10,11,30 The activity of the cells in the device was not affected under a 540 mV/mm dcEF within 8 h. However, an EF strength larger than 900 mV/mm caused cell death in a few hours. Without the dcEF treatment, the migration of CL1-5 cells was random.…”

Section: Resultsmentioning

confidence: 99%

Modulating chemotaxis of lung cancer cells by using electric fields in a microfluidic device

et al. 2014

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We employed direct-current electric fields (dcEFs) to modulate the chemotaxis of lung cancer cells in a microfluidic cell culture device that incorporates both stable concentration gradients and dcEFs. We found that the chemotaxis induced by a 0.5 lM/mm concentration gradient of epidermal growth factor can be nearly compensated by a 360 mV/mm dcEF. When the effect of chemical stimulation was balanced by the electrical drive, the cells migrated randomly, and the path lengths were largely reduced. We also demonstrated electrically modulated chemotaxis of two types of lung cancer cells with opposite directions of electrotaxis in this device. V C 2014 AIP Publishing LLC. [http://dx

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“…"All the electric phenomena which it manifests being due to internal molecular changes associated with activity or injury" (in his work Researches on Animal Electricity, from 1848 to 1884). Micro-electric current had been detected in wounds in both epithelial and non-epithelial tissues in human and other mammals using various modern techniques [84][85][86][87][88][89][90][91][92]. Sta et al [84] and Nuccitelli et al [85] reported the endogenous lateral electric fields around corneal and other epithelial lesions.…”

Section: The Identity Of Electric Field Lateralization Induced By Dismentioning

confidence: 99%

“…Micro-electric current had been detected in wounds in both epithelial and non-epithelial tissues in human and other mammals using various modern techniques [84][85][86][87][88][89][90][91][92]. Sta et al [84] and Nuccitelli et al [85] reported the endogenous lateral electric fields around corneal and other epithelial lesions. Song et al [86] detailed the features: "In cornea and skin, a laterally oriented, wound-induced d.c. (direct current) electric field is generated instantaneously when the epithelium is damaged, and it persists until re-epithelialization restores the electrical resistance barrier function of the epithelium".…”

Section: The Identity Of Electric Field Lateralization Induced By Dismentioning

confidence: 99%

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Spontaneous high-frequency action potential

Shen

Choe

2011

Sci. China Life Sci.

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Action potential, which is the foundation of physiology and electrophysiology, is most vital in physiological research. This work starts by detecting cardiac electrophysiology (tachyarrhythmias), combined with all spontaneous discharge phenomena in vivo such as wound currents and spontaneous neuropathic pain, elaborates from generation, induction, initiation, to all of the features of spontaneous high-frequency action potential--SSL action potential mechanism, i.e., connecting-end hyperpolarization initiates spontaneous depolarization and action potential in somatic membrane. This work resolves the conundrums of in vivo spontaneous discharge in tachyarrhythmias, wounds, denervation supersensitivity, neurogenic pain (hyperalgesia and allodynia), epileptic discharge and diabetic pain in pathophysiological and clinical researches that have puzzled people for a hundred years. action potential, spontaneous high-frequency action potential, tachyarrhythmias, atrial fibrillation, wound, denervation supersensitivity, neurogenic pain, hyperalgesia and allodynia, epileptic discharge, diabetic pain, regeneration and development Citation:Shen H Y, Choe W C. Spontaneous high-frequency action potential. Sci China Life Sci, 2011Sci, , 54: 311 -335, doi: 10.1007 Wound, nerve disconnection, and atrial fibrillation (AF) induced by the excessive atrial dilation, are commonly characterized by the spontaneous repetitive discharge. Their common induction is the disconnection of intercellular connection, and their common result is the initiation of spontaneous high-frequency discharge, which discloses the existence of the special action of intercellular connection.The Hodgkin-Huxley model has predicted, and the computer models in applied mathematics have well demonstrated, that potassium leakage causes persistent spontaneous electrifying state with spontaneous oscillation of high-frequency action potential. The sustained disconnection of connecting-end space induces potassium leakage in the connecting-end and consequently the sustained reduction of [K + ] i , which induces in vivo spontaneous high-frequency action potential in plasmalemma.To form an intercellular conduction, connecting-end space exerts action on ion diffusions, the alteration of the space alters ion diffusions (i.e., ionic permeability) in the connecting-end. The abolishment of connecting-end space action causes K + leakage and consequently the reduction of intracellular positive electropotential (IPE) (i.e., the increase of intracellular negative potential), which elevates resting somatic membrane potential and initiates action potential in somatic membrane. SSL action potential is named to the course from the initiation (i.e., connecting-end hyperpolarization) to the termination of somatic membrane action potential.Tachyarrhythmias that are characterized by spontaneous discharge have been most deeply studied. Their inductions contain both mechanical actions and chemical actions, and their courses contain the transformation from traditional action potential to SSL-ty...

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Endogenous lateral electric fields around bovine corneal lesions are necessary for and can enhance normal rates of wound healing

Cited by 70 publications

References 10 publications

Cyclic AMP mediates keratinocyte directional migration in an electric field

Cyclic AMP mediates keratinocyte directional migration in an electric field

Modulating chemotaxis of lung cancer cells by using electric fields in a microfluidic device

Spontaneous high-frequency action potential

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