학술논문
Electrically stimulated in vitro heart cell mimic of acute exercise reveals novel immediate cellular responses to exercise: Reduced contractility and metabolism, but maintained calcium cycling and increased myofilament calcium sensitivity.
Document Type
Academic Journal
Author
Costa ADS; School of Cardiovascular and Metabolic Health, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.; Graduate School, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.; Ghouri I; School of Cardiovascular and Metabolic Health, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.; Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.; Johnston A; School of Cardiovascular and Metabolic Health, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.; McGlynn K; School of Cardiovascular and Metabolic Health, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.; McNair A; School of Cardiovascular and Metabolic Health, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.; Bowman P; School of Cardiovascular and Metabolic Health, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.; Malik N; School of Cardiovascular and Metabolic Health, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.; Hurren J; School of Cardiovascular and Metabolic Health, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.; Bingelis T; School of Cardiovascular and Metabolic Health, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.; Dunne M; School of Cardiovascular and Metabolic Health, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.; Smith GL; School of Cardiovascular and Metabolic Health, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.; Kemi OJ; School of Cardiovascular and Metabolic Health, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
Source
Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 8305874 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1099-0844 (Electronic) Linking ISSN: 02636484 NLM ISO Abbreviation: Cell Biochem Funct Subsets: MEDLINE
Subject
Language
English
Abstract
Cardiac cellular responses to acute exercise remain undescribed. We present a model for mimicking acute aerobic endurance exercise to freshly isolated cardiomyocytes by evoking exercise-like contractions over prolonged periods of time with trains of electrical twitch stimulations. We then investigated immediate contractile, Ca 2+ , and metabolic responses to acute exercise in perfused freshly isolated left ventricular rat cardiomyocytes, after a matrix-design optimized protocol and induced a mimic for acute aerobic endurance exercise by trains of prolonged field twitch stimulations. Acute exercise decreased cardiomyocyte fractional shortening 50%-80% (p < .01). This was not explained by changes to intracellular Ca 2+ handling (p > .05); rather, we observed a weak insignificant Ca 2+ transient increase (p = .11), while myofilament Ca 2+ sensitivity increased 20%-70% (p < .05). Acidic pH 6.8 decreased fractional shortening 20%-70% (p < .05) because of 20%-30% decreased Ca 2+ transients (p < .05), but no difference occurred between control and acute exercise (p > .05). Addition of 1 or 10 mM La - increased fractional shortening in control (1 mM La - : no difference, p > .05; 10 mM La - : 20%-30%, p < .05) and acute exercise (1 mM La - : 40%-90%, p < .01; 10 mM La - : 50%-100%, p < .01) and rendered acute exercise indifferent from control (p > .05). Intrinsic autofluorescence showed a resting NAD state of 0.59 ± 0.04 and FAD state of 0.17 ± 0.03, while acute exercise decreased NADH/FAD ratio 8% (p < .01), indicating intracellular oxidation. In conclusion, we show a novel approach for studying immediate acute cardiomyocyte responses to aerobic endurance exercise. We find that acute exercise in cardiomyocytes decreases contraction, but Ca 2+ handling and myofilament Ca 2+ sensitivity compensate for this, while acidosis and reduced energy substrate and mitochondrial ATP generation explain this.
(© 2023 The Authors. Cell Biochemistry and Function published by John Wiley & Sons Ltd.)
(© 2023 The Authors. Cell Biochemistry and Function published by John Wiley & Sons Ltd.)