Ageing is associated with deterioration of calcium homeostasis in isolated human right atrial myocytes

Adela Herraiz-Martínez, Jesus Álvarez-García, Anna Llach, Cristina E. Molina, Jacqueline Fernandes, Andreu Ferrero-Gregori, Cristina Rodríguez, Alexander Vallmitjana, Raul Benítez, Josep M. Padró, Jose Martínez-González, Juan Cinca, Leif Hove-Madsen

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)76-86
Number of pages11
JournalCardiovascular Research
Volume106
Issue number1
DOIs
StatePublished - 1 Apr 2015
Externally publishedYes

Keywords

  • Atrial fibrillation
  • Calsequestrin-2
  • L-type calcium current
  • SERCA2
  • Sarcoplasmic reticulum calcium release

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