title: Ageing is associated with deterioration of calcium homeostasis in isolated human right atrial myocytes.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Cardiovascular Research Centre CSIC-ICCC and IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, St Antoni Mª Claret 167, Barcelona 08025, Spain.
authors.forename: Adela
authors.initials: A
authors.lastname: Herraiz-Martínez
authors.affiliation: Department of Cardiology, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Jesus
authors.initials: J
authors.lastname: Álvarez-García
authors.affiliation: Department of Cardiology, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Llach
authors.affiliation: Cardiovascular Research Centre CSIC-ICCC and IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, St Antoni Mª Claret 167, Barcelona 08025, Spain.
authors.forename: Cristina E
authors.initials: CE
authors.lastname: Molina
authors.affiliation: Department of Cardiology, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Fernandes
authors.affiliation: Department of Cardiology, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Andreu
authors.initials: A
authors.lastname: Ferrero-Gregori
authors.affiliation: Cardiovascular Research Centre CSIC-ICCC and IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, St Antoni Mª Claret 167, Barcelona 08025, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Rodríguez
authors.affiliation: Department of Automatic Control, Universitat Politècnica de Catalunya, Barcelona, Spain.
authors.forename: Alexander
authors.initials: A
authors.lastname: Vallmitjana
authors.affiliation: Department of Automatic Control, Universitat Politècnica de Catalunya, Barcelona, Spain.
authors.forename: Raúl
authors.initials: R
authors.lastname: Benítez
authors.affiliation: Department of Cardiac Surgery, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Padró
authors.affiliation: Cardiovascular Research Centre CSIC-ICCC and IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, St Antoni Mª Claret 167, Barcelona 08025, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Martínez-González
authors.affiliation: Department of Cardiology, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Cinca
authors.affiliation: Cardiovascular Research Centre CSIC-ICCC and IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, St Antoni Mª Claret 167, Barcelona 08025, Spain lhove@csic-iccc.org.
authors.forename: Leif
authors.initials: L
authors.lastname: Hove-Madsen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002155:Calsequestrin / Q000378:metabolism; D005260:Female; D006325:Heart Atria / Q000166:cytology / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000502:physiology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism
chemical_list: C443109:CASQ2 protein, human; D020746:Calcium Channels, L-Type; D002155:Calsequestrin; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506946:ATP2A2 protein, human; D002118:Calcium
keywords: Atrial fibrillation; Calsequestrin-2; L-type calcium current; SERCA2; Sarcoplasmic reticulum calcium release