Da Silva Costa, Ana and Ghouri, Iffath and Johnston, Alexander and Mcglynn, Karen and McNair, Andrew and Bowman, Peter and Malik, Natasha and Hurren, Johanne and Bingelis, Tomas and Dunne, Michael and Smith, Godfrey L. and Kemi, Ole J. (2023) 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. Cell Biochemistry and Function, 41 (8). pp. 1147-1161. ISSN 0263-6484

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, Ca2+, 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 Ca2+ handling (p > .05); rather, we observed a weak insignificant Ca2+ transient increase (p = .11), while myofilament Ca2+ sensitivity increased 20%–70% (p < .05). Acidic pH 6.8 decreased fractional shortening 20%–70% (p < .05) because of 20%–30% decreased Ca2+ 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 NADstate of 0.59 ± 0.04 and FADstate 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 Ca2+ handling and myofilament Ca2+ sensitivity compensate for this, while acidosis and reduced energy substrate and mitochondrial ATP generation explain this.

People
Da Silva Costa, Ana
Author

Da Silva Costa, Ana and Ghouri, Iffath and Johnston, Alexander and Mcglynn, Karen and McNair, Andrew and Bowman, Peter and Malik, Natasha and Hurren, Johanne and Bingelis, Tomas and Dunne, Michael and Smith, Godfrey L. and Kemi, Ole J. (2023) 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. Cell Biochemistry and Function, 41 (8). pp. 1147-1161. ISSN 0263-6484

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Ghouri, Iffath
Author

Da Silva Costa, Ana and Ghouri, Iffath and Johnston, Alexander and Mcglynn, Karen and McNair, Andrew and Bowman, Peter and Malik, Natasha and Hurren, Johanne and Bingelis, Tomas and Dunne, Michael and Smith, Godfrey L. and Kemi, Ole J. (2023) 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. Cell Biochemistry and Function, 41 (8). pp. 1147-1161. ISSN 0263-6484

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Johnston, Alexander
Author

Elbassioni, Ali Ali Mohamed and Raheem, Anmar A. and Song, Jian and Johnston, Alexander S. and Trivett, Cara and Lin, Hong and Zhang, Haobo and Bradley, Ashley and Higgins, Erin and Mooney, Leanne and Koay, Yen Chin and O'Toole, Dylan and Herzyk, Pawel and Nixon, Colin and Blyth, Karen and O'Sullivan, John F. and Lang, Ninian N. and Berry, Colin and Braun, Thomas and Schiattarella, Gabriele G. and Giacca, Mauro and McBride, Martin W. and Nicklin, Stuart A. and Cameron, Ewan R. and Loughrey, Christopher M. and MacDonald, Eilidh A. (2025) Targeting Runx1 protects against heart failure with preserved ejection fraction. bioRxiv.

Da Silva Costa, Ana and Ghouri, Iffath and Johnston, Alexander and Mcglynn, Karen and McNair, Andrew and Bowman, Peter and Malik, Natasha and Hurren, Johanne and Bingelis, Tomas and Dunne, Michael and Smith, Godfrey L. and Kemi, Ole J. (2023) 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. Cell Biochemistry and Function, 41 (8). pp. 1147-1161. ISSN 0263-6484

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Mcglynn, Karen
Author

Da Silva Costa, Ana and Ghouri, Iffath and Johnston, Alexander and Mcglynn, Karen and McNair, Andrew and Bowman, Peter and Malik, Natasha and Hurren, Johanne and Bingelis, Tomas and Dunne, Michael and Smith, Godfrey L. and Kemi, Ole J. (2023) 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. Cell Biochemistry and Function, 41 (8). pp. 1147-1161. ISSN 0263-6484

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McNair, Andrew
Author

Da Silva Costa, Ana and Ghouri, Iffath and Johnston, Alexander and Mcglynn, Karen and McNair, Andrew and Bowman, Peter and Malik, Natasha and Hurren, Johanne and Bingelis, Tomas and Dunne, Michael and Smith, Godfrey L. and Kemi, Ole J. (2023) 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. Cell Biochemistry and Function, 41 (8). pp. 1147-1161. ISSN 0263-6484

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Bowman, Peter
Author

Da Silva Costa, Ana and Ghouri, Iffath and Johnston, Alexander and Mcglynn, Karen and McNair, Andrew and Bowman, Peter and Malik, Natasha and Hurren, Johanne and Bingelis, Tomas and Dunne, Michael and Smith, Godfrey L. and Kemi, Ole J. (2023) 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. Cell Biochemistry and Function, 41 (8). pp. 1147-1161. ISSN 0263-6484

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Malik, Natasha
Author

Da Silva Costa, Ana and Ghouri, Iffath and Johnston, Alexander and Mcglynn, Karen and McNair, Andrew and Bowman, Peter and Malik, Natasha and Hurren, Johanne and Bingelis, Tomas and Dunne, Michael and Smith, Godfrey L. and Kemi, Ole J. (2023) 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. Cell Biochemistry and Function, 41 (8). pp. 1147-1161. ISSN 0263-6484

Malik, Natasha and Hay, Jodie and Almuhanna, Hassan N.B. and Dunn, Karen M. and Lees, Jamie and Cassels, Jennifer and Li, Jiatian and Nakagawa, Rinako and Sansom, Owen J. and Michie, Alison M. (2023) mTORC1-selective activation of translation elongation promotes disease progression in chronic lymphocytic leukemia. Leukemia, 37. pp. 2414-2425. ISSN 0887-6924

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Hurren, Johanne
Author

Da Silva Costa, Ana and Ghouri, Iffath and Johnston, Alexander and Mcglynn, Karen and McNair, Andrew and Bowman, Peter and Malik, Natasha and Hurren, Johanne and Bingelis, Tomas and Dunne, Michael and Smith, Godfrey L. and Kemi, Ole J. (2023) 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. Cell Biochemistry and Function, 41 (8). pp. 1147-1161. ISSN 0263-6484

See full publications list
Bingelis, Tomas
Author

Da Silva Costa, Ana and Ghouri, Iffath and Johnston, Alexander and Mcglynn, Karen and McNair, Andrew and Bowman, Peter and Malik, Natasha and Hurren, Johanne and Bingelis, Tomas and Dunne, Michael and Smith, Godfrey L. and Kemi, Ole J. (2023) 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. Cell Biochemistry and Function, 41 (8). pp. 1147-1161. ISSN 0263-6484

See full publications list
Dunne, Michael
Author

Da Silva Costa, Ana and Ghouri, Iffath and Johnston, Alexander and Mcglynn, Karen and McNair, Andrew and Bowman, Peter and Malik, Natasha and Hurren, Johanne and Bingelis, Tomas and Dunne, Michael and Smith, Godfrey L. and Kemi, Ole J. (2023) 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. Cell Biochemistry and Function, 41 (8). pp. 1147-1161. ISSN 0263-6484

See full publications list
Smith, Godfrey L.
Author

Da Silva Costa, Ana and Ghouri, Iffath and Johnston, Alexander and Mcglynn, Karen and McNair, Andrew and Bowman, Peter and Malik, Natasha and Hurren, Johanne and Bingelis, Tomas and Dunne, Michael and Smith, Godfrey L. and Kemi, Ole J. (2023) 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. Cell Biochemistry and Function, 41 (8). pp. 1147-1161. ISSN 0263-6484

See full publications list
Kemi, Ole J.
Author

Da Silva Costa, Ana and Ghouri, Iffath and Johnston, Alexander and Mcglynn, Karen and McNair, Andrew and Bowman, Peter and Malik, Natasha and Hurren, Johanne and Bingelis, Tomas and Dunne, Michael and Smith, Godfrey L. and Kemi, Ole J. (2023) 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. Cell Biochemistry and Function, 41 (8). pp. 1147-1161. ISSN 0263-6484

See full publications list
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