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Updated: May 5, 2026
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Multi-parameter Measurement of the Permeability Transition Pore Opening in Isolated Mouse Heart Mitochondria
Published on: September 7, 2012
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Transient mitochondrial permeability transition pore opening mediates preconditioning-induced protection
Derek Hausenloy1, Abigail Wynne, Michael Duchen
1The Hatter Institute and Centre for Cardiology, University College London, UK.
Circulation
|April 7, 2004
Summary
Transient opening of the mitochondrial permeability transition pore (mPTP) and reactive oxygen species (ROS) are key to cardioprotection from preconditioning and uncoupling. Inhibiting mPTP or ROS abolishes these protective effects.
Area of Science:
- Cardiovascular Research
- Mitochondrial Physiology
- Cellular Signaling
Background:
- Transient opening of the mitochondrial permeability transition pore (mPTP) influences mitochondrial calcium levels and reactive oxygen species (ROS) signaling.
- This transient mPTP opening is hypothesized to mediate protective effects observed in myocardial preconditioning and mitochondrial uncoupling.
Purpose of the Study:
- To investigate the role of transient mPTP opening and ROS in mediating the protective effects of myocardial preconditioning and mitochondrial uncoupling.
Main Methods:
- Isolated perfused rat hearts underwent ischemia/reperfusion injury.
- The infarct-risk-volume ratio was assessed after interventions.
- Pharmacological agents were used to inhibit mPTP opening (cyclosporine-A, sanglifehrin-A) or ROS (N-mercaptopropionylglycine) during preconditioning protocols.
- Diazoxide, CCPA, and 2,4-dinitrophenol were used for pharmacological preconditioning and mitochondrial uncoupling.
Main Results:
- Inhibition of mPTP opening during preconditioning abolished the protective effects of ischemic preconditioning (IPC), diazoxide, CCPA, and 2,4-dinitrophenol.
- Inhibition of ROS abolished the protective effects of IPC, diazoxide, and 2,4-dinitrophenol, but not CCPA.
- Diazoxide induced CsA-sensitive, transient mPTP opening in adult rat myocytes.
Conclusions:
- The protective effects of IPC, diazoxide, and mitochondrial uncoupling are dependent on transient mPTP opening.
- ROS signaling is also crucial for the protective mechanisms mediated by IPC, diazoxide, and mitochondrial uncoupling.
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