title: Electrical stimulation of cardiomyocytes activates mitochondrial matrix metalloproteinase causing electrical remodeling.
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.
authors.affiliation: Department of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, KY 40202, United States.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Vacek
authors.forename: Naira
authors.initials: N
authors.lastname: Metreveli
authors.forename: Neetu
authors.initials: N
authors.lastname: Tyagi
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Vacek
authors.forename: Sebastian
authors.initials: S
authors.lastname: Pagni
authors.forename: Suresh C
authors.initials: SC
authors.lastname: Tyagi
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D004558:Electric Stimulation; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008929:Mitochondria, Heart / Q000201:enzymology*; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000201:enzymology / Q000502:physiology*
chemical_list: D020780:Matrix Metalloproteinase 9; D002118:Calcium