Ionic Components of Electric Current at Rat Corneal Wounds

Ionic Components of Electric Current at Rat Corneal Wounds

Autor Vieira, Ana Carolina Autor UNIFESP Google Scholar
Reid, Brian Google Scholar
Cao, Lin Google Scholar
Mannis, Mark J. Google Scholar
Schwab, Ivan R. Google Scholar
Zhao, Min Google Scholar
Instituição Univ Calif Davis
Universidade Federal de São Paulo (UNIFESP)
Resumo Background: Endogenous electric fields and currents occur naturally at wounds and are a strong signal guiding cell migration into the wound to promote healing. Many cells involved in wound healing respond to small physiological electric fields in vitro. It has long been assumed that wound electric fields are produced by passive ion leakage from damaged tissue. Could these fields be actively maintained and regulated as an active wound response? What are the molecular, ionic and cellular mechanisms underlying the wound electric currents?Methodology/Principal Findings: Using rat cornea wounds as a model, we measured the dynamic timecourses of individual ion fluxes with ion-selective probes. We also examined chloride channel expression before and after wounding. After wounding, Ca(2+) efflux increased steadily whereas K(+) showed an initial large efflux which rapidly decreased. Surprisingly, Na(+) flux at wounds was inward. A most significant observation was a persistent large influx of Cl(-), which had a time course similar to the net wound electric currents we have measured previously. Fixation of the tissues abolished ion fluxes. Pharmacological agents which stimulate ion transport significantly increased flux of Cl(-), Na(+) and K(+). Injury to the cornea caused significant changes in distribution and expression of Cl(-) channel CLC2.Conclusions/Significance: These data suggest that the outward electric currents occurring naturally at corneal wounds are carried mainly by a large influx of chloride ions, and in part by effluxes of calcium and potassium ions. Ca(2+) and Cl(-) fluxes appear to be mainly actively regulated, while K(+) flux appears to be largely due to leakage. the dynamic changes of electric currents and specific ion fluxes after wounding suggest that electrical signaling is an active response to injury and offers potential novel approaches to modulate wound healing, for example eye-drops targeting ion transport to aid in the challenging management of non-healing corneal ulcers.
Idioma Inglês
Financiador National Institutes of Health National Eye Institute
Wellcome Trust
Research to Prevent Blindness, Inc.
UC Davis Dermatology Department
California Institute of Regenerative Medicine
Número do financiamento National Institutes of Health National Eye Institute: 1R01EY019101
Wellcome Trust: 068012
NSFC: 30628026
California Institute of Regenerative Medicine: RB1-01417
NSF: MCB-0951199
Data 2011-02-25
Publicado em Plos One. San Francisco: Public Library Science, v. 6, n. 2, 12 p., 2011.
ISSN 1932-6203 (Sherpa/Romeo, fator de impacto)
Editor Public Library Science
Extensão 12
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000287764100057

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