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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.|
Rodrigo, Glenn C.
|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.|
|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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