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

Da Silva Costa, A. et al. (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. (doi: 10.1002/cbf.3847) (PMID:37665041)

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.

• Item Type: Articles
• Additional Information: Funding information: Biotechnology and Biological Sciences Research Council; British Heart Foundation, Grant/Award Number: PG/09/107; Physiological Society.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McNair, Mr Andrew and Johnston, Dr Alexander and Smith, Professor Godfrey and Mcglynn, Miss Karen and Da Silva Costa, Dr Ana and Bowman, Mr Peter and Malik, Miss Natasha and Ghouri, Dr Iffath and Kemi, Dr Ole
• Authors: Da Silva Costa, A., Ghouri, I., Johnston, A., Mcglynn, K., McNair, A., Bowman, P., Malik, N., Hurren, J., Bingelis, T., Dunne, M., Smith, G. L., and Kemi, O. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences; College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Cell Biochemistry and Function
• Publisher: Wiley
• ISSN: 0263-6484
• ISSN (Online): 1099-0844
• Published Online: 04 September 2023
• Copyright Holders: Copyright: © 2023 The Authors
• First Published: First published in Cell Biochemistry and Function 41(8):1147-1161
• Publisher Policy: Reproduced under a Creative Commons licence

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
163118		Cardiac CaMK in heart failure and exercise training	Ole Kemi	British Heart Foundation (BHF)	PG/09/107	School of Cardiovascular & Metabolic Health