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A Flow Cytometry-based Assay for Measuring Mitochondrial Membrane Potential in Cardiac Myocytes After Hypoxia/Reoxygenation
Published on: July 13, 2018
The mitochondrial origin of postischemic arrhythmias
Fadi G Akar1, Miguel A Aon, Gordon F Tomaselli
1Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 210205, USA.
The Journal of Clinical Investigation
|November 15, 2005
Summary
Mitochondrial inner membrane potential instability during heart ischemia-reperfusion promotes arrhythmias. Blocking the mitochondrial benzodiazepine receptor (mBzR) with 4-chlorodiazepam stabilizes this potential, preventing abnormal electrical activity and ventricular fibrillation.
Area of Science:
- Cardiology
- Mitochondrial Physiology
- Electrophysiology
Background:
- Mitochondrial inner membrane potential (DeltaPsi(m)) recovery is crucial for post-heart attack functional recovery.
- Mitochondrial ROS-induced ROS release collapses DeltaPsi(m) and destabilizes action potential (AP) via an inner membrane anion channel (IMAC) modulated by the mitochondrial benzodiazepine receptor (mBzR).
Purpose of the Study:
- To test if the mBzR-IMAC mechanism contributes to DeltaPsi(m) heterogeneity during ischemia-reperfusion (IR).
- To determine if this mechanism promotes abnormal electrical activation and arrhythmias in the whole heart.
Main Methods:
- High-resolution optical AP mapping in guinea pig hearts subjected to global ischemia and reperfusion.
- Pharmacological intervention using mBzR antagonist (4'-chlorodiazepam) and agonist.
Main Results:
- Control hearts showed typical IR electrophysiological changes, including AP shortening and reperfusion ventricular fibrillation.
- 4'-chlorodiazepam treatment reduced AP shortening and prevented reperfusion arrhythmias, even when given just before reperfusion.
- mBzR agonist exacerbated IR-induced changes and failed to prevent arrhythmias.
Conclusions:
- DeltaPsi(m) instability is directly linked to the heterogeneous electrophysiological substrate of the postischemic heart.
- The mitochondrial membrane represents a novel therapeutic target for preventing arrhythmias in ischemic heart disease.
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