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Mitochondrial targets for arrhythmia suppression: is there a role for pharmacological intervention?

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Journal of Interventional Cardiac Electrophysiology Aims and scope Submit manuscript

Abstract

Mitochondrial dysfunction is a hallmark of common cardiovascular disorders, including ischemia–reperfusion injury, hypertrophy, heart failure, and diabetes mellitus. While the role of the mitochondrial network in regulating energy production and cell death pathways is well established, its active control of other critical cellular functions, including excitation–contraction coupling and excitability, is less understood. The purpose of this focused review article is to highlight the growing mechanistic link between mitochondrial dysfunction and arrhythmogenesis. The goal is not to provide a comprehensive listing of all factors by which mitochondrial bioenergetics and altered cellular redox status affect ion channel function but rather to focus on one central mechanism of arrhythmogenesis which arises from a mitochondrial origin. In doing so, we discuss the role of mitochondrial targets for suppressing arrhythmias through this mechanism.

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Abbreviations

I/R:

Ischemia–reperfusion injury

LVH:

Left ventricular hypertrophy

HF:

Heart failure

MI:

Myocardial infarction

AP:

Action potential

APD:

Action potential duration

ETC:

Electron transport chain

ATP:

Adenine triphosphate

DYm:

Mitochondrial membrane potential

ROS:

Reactive oxygen species

H2O2 :

Hydrogen peroxide

O2 − :

Superoxide anion

RIRR:

ROS-induced ROS release

OS:

Oxidative stress

sarcKATP :

Sarcolemmal ATP-sensitive potassium channels

mPTP:

Mitochondrial permeability transition pore

CsA:

Cyclosporine-A

IMAC:

Inner membrane anion channel

4′-Cl-DZP:

4′-Chlorodiazepam (IMAC blocker)

mBzR:

Mitochondrial benzodiazepine receptor

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  1. Cardiovascular Institute, Icahn School of Medicine, Mount Sinai Medical Center, New York, NY, USA

    Fadi G. Akar

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Akar, F.G. Mitochondrial targets for arrhythmia suppression: is there a role for pharmacological intervention?. J Interv Card Electrophysiol 37, 249–258 (2013). https://doi.org/10.1007/s10840-013-9809-3

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  • DOI: https://doi.org/10.1007/s10840-013-9809-3

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