Riding and Pullar corrected purinergic receptors and keratinocyte galvanotaxis JCP 2015.pdf (2.06 MB)

ATP release and P2Y receptor signalling are essential for keratinocyte galvanotaxis

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journal contribution
posted on 18.06.2015 by Aimie Riding, Christine E. Pullar
Repair to damaged tissue requires directional cell migration to heal the wound. Immediately upon wounding an electrical guidance cue is created with the cathode of the electric field (EF) located at the center of the wound. Previous research has demonstrated directional migration of keratinocytes towards the cathode when an EF of physiological strength (100–150 mV/mm) is applied in vitro, but the “sensor” by which keratinocytes sense the EF remains elusive. Here we use a customised chamber design to facilitate the application ofa direct current (DC) EF of physiological strength (100 mV/mm) to keratinocytes whilst pharmacologically modulating the activation ofboth connexin hemichannels and purinergic receptorsto determine their role inEF-mediated directional keratinocyte migration, galvanotaxis. In addition, keratinocytes were exposed to DiSCAC2(3) dye to visualize membrane potential changes within the cell upon exposure to the applied DC EF. Here we unveil ATP-medicated mechanisms that underpin the initiation of keratinocyte galvanotaxis. The application of a DC EF of 100 mV/mm releases ATP via hemichannels activatinga subset of purinergic P2Y receptors, locally, to initiate the directional migration of keratinocytes towards the cathodein vitro, the center of the woundin vivo. The delineation of the mechanisms underpinning galvanotaxis extends our understanding of this endogenous cue and will facilitate the optimization and wider use of EF devices for chronic wound treatment. This article is protected by copyright. All rights reserved

Funding

Wellcome Trust; contract grant number: 82586.

History

Citation

Journal of Cellular Physiology 2015 1097-4652

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Biological Sciences/Department of Cell Physiology and Pharmacology

Version

AM (Accepted Manuscript)

Published in

Journal of Cellular Physiology 2015 1097-4652

Publisher

Wiley for Wiley-Liss

issn

0021-9541

eissn

1097-4652

Copyright date

2015

Available date

08/06/2016

Publisher version

http://onlinelibrary.wiley.com/doi/10.1002/jcp.25070/abstract

Language

en

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