Ageing is associated with deterioration of calcium homeostasis in isolated human right atrial myocytes
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Ageing is associated with deterioration of calcium homeostasis in isolated human right atrial myocytes. / Herraiz-Martínez, Adela; Álvarez-García, Jesus; Llach, Anna; Molina, Cristina E; Fernandes, Jacqueline; Ferrero-Gregori, Andreu; Rodríguez, Cristina; Vallmitjana, Alexander; Benítez, Raúl; Padró, Josep M; Martínez-González, José; Cinca, Juan; Hove-Madsen, Leif.
in: CARDIOVASC RES, Jahrgang 106, Nr. 1, 01.04.2015, S. 76-86.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Ageing is associated with deterioration of calcium homeostasis in isolated human right atrial myocytes
AU - Herraiz-Martínez, Adela
AU - Álvarez-García, Jesus
AU - Llach, Anna
AU - Molina, Cristina E
AU - Fernandes, Jacqueline
AU - Ferrero-Gregori, Andreu
AU - Rodríguez, Cristina
AU - Vallmitjana, Alexander
AU - Benítez, Raúl
AU - Padró, Josep M
AU - Martínez-González, José
AU - Cinca, Juan
AU - Hove-Madsen, Leif
N1 - © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.
PY - 2015/4/1
Y1 - 2015/4/1
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Aging
KW - Calcium
KW - Calcium Channels, L-Type
KW - Calsequestrin
KW - Female
KW - Heart Atria
KW - Homeostasis
KW - Humans
KW - Male
KW - Middle Aged
KW - Myocardial Contraction
KW - Myocytes, Cardiac
KW - Patch-Clamp Techniques
KW - Sarcoplasmic Reticulum
KW - Sarcoplasmic Reticulum Calcium-Transporting ATPases
KW - Comparative Study
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1093/cvr/cvv046
DO - 10.1093/cvr/cvv046
M3 - SCORING: Journal article
C2 - 25712961
VL - 106
SP - 76
EP - 86
JO - CARDIOVASC RES
JF - CARDIOVASC RES
SN - 0008-6363
IS - 1
ER -