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|Title:||ATP release and P2Y receptor signalling are essential for keratinocyte galvanotaxis|
Pullar, Christine E.
|Publisher:||Wiley for Wiley-Liss|
|Citation:||Journal of Cellular Physiology 2015 1097-4652|
|Abstract:||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|
|Rights:||Archived with reference to SHERPA/RoMEO and publisher website. This is the peer reviewed version of the following article: Journal of Cellular Physiology 2015 1097-4652, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1002/jcp.25070/abstract. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.|
|Appears in Collections:||Published Articles, Dept. of Cancer Studies and Molecular Medicine|
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|Riding and Pullar corrected purinergic receptors and keratinocyte galvanotaxis JCP 2015.pdf||Post-review (final submitted)||2.11 MB||Adobe PDF||View/Open|
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