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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
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 (, 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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