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Updated: Jun 5, 2026
Simultaneous Electrical and Mechanical Stimulation to Enhance Cells' Cardiomyogenic Potential
Published on: January 18, 2019
Electrical stimulation of cardiomyocytes activates mitochondrial matrix metalloproteinase causing electrical
Thomas P Vacek1, Naira Metreveli, Neetu Tyagi
1Department of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, KY 40202, United States.
Abstract:
Cardiac arrhythmias, instigated by mechanical and electrical remodeling, are associated with activation of extracellular matrix metalloproteinases (MMPs). However, the connection between intracellular MMPs activation and arrhythmogenesis is not well established. Previously, we determined localization of MMP in the mitochondria using confocal microscopy. We tested the hypothesis that electrical pacing induces the activation of mitochondrial MMP (mtMMP) and is associated with myocyte mechanical dysfunction. Myocytes were isolated and field stimulated at 1 and 4 Hz. Myocyte mechanics and calcium transient was studied using Ion-Optix system. Mitochondrial MMP-9 activation was evaluated using zymography. There was a 25% increase in 1 Hz and 40% increase in 4 Hz stimulation. We observed an increase in mtMMP activation with increase in electrical pacing compared to 0 Hz with a significant increase (p<0.05, n=3). Field stimulation at 4 Hz decreased cell re-lengthening. The levels of calcium transient were reduced with increase in contraction frequency. We conclude that electrical stimulation activates mtMMP-9 that is associated with myocyte mechanical dysfunction.
Insights
Electrical stimulation activates mitochondrial matrix metalloproteinases-9 (mtMMP-9), contributing to heart muscle cell dysfunction and potentially cardiac arrhythmias.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Cellular Electrophysiology
Background:
- Cardiac arrhythmias are linked to extracellular matrix metalloproteinases (MMPs) and cellular remodeling.
- The role of intracellular MMPs, particularly mitochondrial MMPs (mtMMPs), in arrhythmogenesis remains unclear.
- Previous research localized MMPs within mitochondria.
Purpose of the Study:
- To investigate the hypothesis that electrical pacing activates mitochondrial MMPs (mtMMPs).
- To determine if mtMMP activation correlates with myocyte mechanical dysfunction.
- To explore the impact of electrical stimulation on mitochondrial MMP-9 activity.
Main Methods:
- Isolation of cardiac myocytes.
- Field stimulation of myocytes at varying frequencies (0 Hz, 1 Hz, 4 Hz).
- Assessment of myocyte mechanics and calcium transients using the Ion-Optix system.
- Evaluation of mitochondrial MMP-9 activation via zymography.
Main Results:
- Electrical stimulation significantly increased mitochondrial MMP-9 activation, with a 25% rise at 1 Hz and 40% at 4 Hz.
- Higher pacing frequencies led to increased mtMMP activation compared to the control (0 Hz).
- 4 Hz stimulation impaired myocyte re-lengthening and reduced calcium transient levels.
Conclusions:
- Electrical stimulation activates mitochondrial MMP-9 (mtMMP-9) in cardiac myocytes.
- Activated mtMMP-9 is associated with impaired myocyte mechanical function.
- This finding suggests a novel mechanism linking electrical activity to cardiac dysfunction via mitochondrial MMPs.
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