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

作者：Herraiz Martinez Adela; Alvarez Garcia Jesus; Llach Anna; Molina Cristina E; Fernandes Jacqueline; Ferrero Gregori Andreu; Rodriguez Cristina; Vallmitjana Alexander; Benitez Raul; Padro Josep M; Martinez Gonzalez Jose; Cinca Juan; Hove Madsen Leif^*

来源：Cardiovascular Research, 2015, 106(1): 76-86.

DOI：10.1093/cvr/cvv046

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

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 (I-Ca) 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.

• 出版日期2015-4-1