Ageing is associated with deterioration of calcium homeostasis in isolated human right atrial myocytes
Por:
Herraiz-Martínez A., Álvarez-García J., Llach A., Molina C.E., Fernandes J., Ferrero-Gregori A., Rodríguez C., Vallmitjana A., Benítez R., Padró J.M., Martínez-González J., Cinca J., Hove-Madsen L.
Publicada:
1 ene 2015
Resumen:
Aims Ageing-related cardiac disorders such as heart failure and atrial fibrillation often present with intracellular calcium homeostasis dysfunction. However, knowledge of the intrinsic effects of ageing on cellular calcium handling in the human heart is sparse. Therefore, this study aimed to analyse how ageing affects key mechanisms that regulate intracellular calcium in human atrial myocytes. Methods and results Whole membrane currents and intracellular calcium transients were measured in isolated human right atrial myocytes from 80 patients with normal left atrial dimensions and no history of atrial fibrillation. Patients were categorized as young (<55 years, n = 21), middle aged (55-74 years, n = 42), and old (=75 years, n = 17). Protein levels were determined by western blot. Ageing was associated with the following electrophysiological changes: (i) a 3.2-fold decrease in the calcium transient (P < 0.01); (ii) reduction of the L-type calcium current (ICa) amplitude (2.4 ± 0.3 pA/pF vs. 1.4 ± 0.2 pA/pF, P < 0.01); (iii) lower levels of L-type calcium channel alpha-subunit (P < 0.05); (iv) lower rates of both fast (14.5 ± 0.9 ms vs. 20.9 ± 1.9, P < 0.01) and slow (73 ± 3 vs. 120 ± 12 ms, P < 0.001) ICa inactivation; and (v) a decrease in the sarcoplasmic reticulum calcium content (10.1 ± 0.8 vs. 6.4 ± 0.6 amol/pF, P < 0.005) associated with a significant decrease in both SERCA2 (P < 0.05) and calsequestrin-2 (P < 0.05) protein levels. In contrast, ageing did not affect spontaneous sarcoplasmic reticulum calcium release. Conclusion Ageing is associated with depression of SR calcium content, L-type calcium current, and calcium transient amplitude that may favour a progressive decline in right atrial contractile function with age. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.
Filiaciones:
Herraiz-Martínez A.:
Cardiovascular Research Centre CSIC-ICCC, IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, St Antoni M Claret 167, Barcelona, 08025, Spain
Álvarez-García J.:
Department of Cardiology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
Llach A.:
Department of Cardiology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
Molina C.E.:
Cardiovascular Research Centre CSIC-ICCC, IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, St Antoni M Claret 167, Barcelona, 08025, Spain
Institute of Pharmacology, Faculty of Medicine, University Duisburg-Essen, Essen, 45122, Germany
Fernandes J.:
Department of Cardiology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
Ferrero-Gregori A.:
Department of Cardiology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
Rodríguez C.:
Cardiovascular Research Centre CSIC-ICCC, IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, St Antoni M Claret 167, Barcelona, 08025, Spain
Vallmitjana A.:
Department of Automatic Control, Universitat Politècnica de Catalunya, Barcelona, Spain
Benítez R.:
Department of Automatic Control, Universitat Politècnica de Catalunya, Barcelona, Spain
Padró J.M.:
Department of Cardiac Surgery, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain
Martínez-González J.:
Cardiovascular Research Centre CSIC-ICCC, IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, St Antoni M Claret 167, Barcelona, 08025, Spain
Cinca J.:
Department of Cardiology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
Hove-Madsen L.:
Cardiovascular Research Centre CSIC-ICCC, IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, St Antoni M Claret 167, Barcelona, 08025, Spain
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