Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/38024
Title: Remote ischemic preconditioning of cardiomyocytes inhibits the mitochondrial permeability transition pore independently of reduced calcium‐loading or sarcKATP channel activation
Authors: Turrell, Helen E.
Thaitirarot, Chokanan
Crumbie, Hayley
Rodrigo, Glenn C.
First Published: 26-Nov-2014
Publisher: Wiley Open Access
Citation: Physiological Reports, 2014, 2, e12231
Abstract: Ischemic preconditioning (IPC) inhibits Ca²⁺‐loading during ischemia which contributes to cardioprotection by inhibiting mechanical injury due to hypercontracture and biochemical injury through mitochondrial permeability transition (MPT) pores during reperfusion. However, whether remote‐IPC reduced Ca²⁺‐loading during ischemia and its subsequent involvement in inhibiting MPT pore formation during reperfusion has not been directly shown. We have developed a cellular model of remote IPC to look at the impact of remote conditioning on Ca²⁺‐regulation and MPT pore opening during simulated ischemia and reperfusion, using fluorescence microscopy. Ventricular cardiomyocytes were isolated from control rat hearts, hearts preconditioned with three cycles of ischemia/reperfusion or naïve myocytes remotely conditioned with effluent collected from preconditioned hearts. Both conventional‐IPC and remote‐IPC reduced the loss of Ca²⁺‐homeostasis and contractile function following reenergization of metabolically inhibited cells and protected myocytes against ischemia/reperfusion injury. However, only conventional‐IPC reduced the Ca²⁺‐loading during metabolic inhibition and this was independent of any change in sarcKATP channel activity but was associated with a reduction in Na⁺‐loading, reflecting a decrease in Na/H exchanger activity. Remote‐IPC delayed opening of the MPT pores in response to ROS, which was dependent on PKCε and NOS‐signaling. These data show that remote‐IPC inhibits MPT pore opening to a similar degree as conventional IPC, however, the contribution of MPT pore inhibition to protection against reperfusion injury is independent of Ca²⁺‐loading in remote IPC. We suggest that inhibition of the MPT pore and not Ca²⁺‐loading is the common link in cardioprotection between conventional and remote IPC.
DOI Link: 10.14814/phy2.12231
ISSN: 2051-817X
Links: http://physreports.physiology.org/content/2/11/e12231
http://hdl.handle.net/2381/38024
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2014. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences

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