Home > Articles > Published articles > Ageing is associated with deterioration of calcium homeostasis in isolated human right atrial myocytes |
Date: | 2015 |
Abstract: | 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. 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 ) 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) I 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. 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. |
Grants: | Ministerio de Ciencia e Innovación SAF2011-30312 Ministerio de Ciencia e Innovación CNIC/2009-08 Ministerio de Ciencia e Innovación DPI2013-44584-R Ministerio de Ciencia e Innovación SAF2012-40127 Instituto de Salud Carlos III RD12/0042-0002 European Commission PIEF-GA-331241 Instituto de Salud Carlos III RD12/0042-0002 |
Note: | Altres ajuts: FEDER/RD12/0042-0053 |
Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. |
Language: | Anglès |
Document: | Article ; recerca ; Versió publicada |
Subject: | L-type calcium current ; SERCA2 ; Calsequestrin-2 ; Sarcoplasmic reticulum calcium release ; Atrial fibrillation |
Published in: | Cardiovascular research, Vol. 106 (february 2015) , p. 76-86, ISSN 1755-3245 |
11 p, 657.4 KB |