alexa Remote Ischemic Preconditioning Cardio-protection via Enhanced Cell Volume Regulation Requires Activation of Swelling-Activated Chloride (Icl-Swell) Channels | Abstract
ISSN: 2329-6607

Cardiovascular Pharmacology: Open Access
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Research Article

Remote Ischemic Preconditioning Cardio-protection via Enhanced Cell Volume Regulation Requires Activation of Swelling-Activated Chloride (Icl-Swell) Channels

Gregory J Wilson1-3*, Krista M Hawrylyshyn1, Silvia Cioci1, Sheena Guglani1 and Roberto J Diaz1,2

1Division of Physiology and Experimental Medicine, Research Institute Toronto, Canada

2Department of Pediatric Laboratory Medicine and Pathology, the Hospital for Sick Children, Toronto, Canada

3Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada

*Corresponding Author:
Gregory J Wilson
Division of Physiology and Experimental Medicine The Hospital for Sick Children
Toronto, Ontario, Canada
Tel: (416)-813-5965
Fax: (416)-813-7480
E-mail: [email protected]

Received date: March 31, 2014; Accepted date: May 03, 2014; Published date: May 11, 2014

Citation: Wilson GJ, Hawrylyshyn KM, Cioci S, Guglani S, Diaz RJ (2014) Remote Ischemic Preconditioning Cardio-protection via Enhanced Cell Volume Regulation Requires Activation of Swelling-Activated Chloride (Icl-Swell) Channels. Cardiol Pharmacol 3:117. doi:10.4172/2329-6607.1000117

Copyright: © 2014 Wilson GJ, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.



We have previously shown that remote ischemic preconditioning induced in cardiomyocytes by a brief direct incubation in rabbit blood dialysate, originated from other rabbits initially subjected to brief periods of limb ischemia/ reperfusion, given prior exposure to a prolonged ischemia/reperfusion protects cardiomyocytes against necrosis. In this study, we examined the hypothesis that sarcolemmal protein kinase C epsilon interacts with the swellingactivated Cl- channel to both enhance cardiomyocyte volume regulation and protect against cardiomyocyte necrosis in limb ischemia/reperfusion remote ischemic preconditioning.


Cultured (forty-eight hours) rabbit cardiomyocytes (control and remote ischemic preconditioned dialysate treated) were, after stabilization, subjected to either thirty-minute hypo-osmotic stress or to seventy-five minutes of simulated ischemia (severe hypoxia plus metabolic inhibition) followed by sixty minutes of simulated reperfusion (in oxygenated media), with or without a specific swelling-activated chloride channel inhibitor or its vehicle given ten minutes prior and during the hypo-osmotic stress or the simulate ischemia, to measure peak cell swelling (between eight to twelve minutes of hypo-osmotic stress), regulatory volume decrease and cell necrosis (by trypan blue staining).


Specific inhibition of swell-activated chloride channels not only substantially inhibited remote ischemic preconditioned dialysate induced protection against cardiomyocyte necrosis but it also significantly impaired cardiomyocyte volume regulation. PKCε was found to co-immunoprecipitate with ClC-3, consistent with this kinase influencing swell-activated chloride channel activity.


These findings indicate that swelling-activated chloride channels are essential for the cardioprotection by remote ischemic preconditioning.


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