Related Experiment Video
Updated: Apr 17, 2026
Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents
Published on: July 3, 2013
Ageing is associated with deterioration of calcium homeostasis in isolated human right atrial myocytes
Adela Herraiz-Martínez1, Jesus Álvarez-García2, Anna Llach2
1Cardiovascular Research Centre CSIC-ICCC and IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, St Antoni Mª Claret 167, Barcelona 08025, Spain.
Insights
Aging significantly impairs cardiac calcium handling in human atrial myocytes. Key changes include reduced calcium transient amplitude and L-type calcium current, potentially impacting heart function.
Area of Science:
- Cardiology
- Cellular Physiology
- Aging Research
Background:
- Ageing-related cardiac disorders like heart failure and atrial fibrillation are linked to intracellular calcium handling dysfunction.
- Limited understanding exists regarding the intrinsic effects of aging on cellular calcium regulation in the human heart.
Purpose of the Study:
- To investigate how aging impacts key mechanisms regulating intracellular calcium in human atrial myocytes.
- To analyze age-related changes in electrophysiological properties and protein expression related to calcium handling.
Main Methods:
- Isolated human right atrial myocytes from 80 patients (categorized by age: young, middle-aged, old) were studied.
- Electrophysiological measurements included whole membrane currents and intracellular calcium transients.
- Protein levels of key calcium-handling proteins were assessed using western blot.
Main Results:
- Aging led to a 3.2-fold decrease in calcium transient amplitude and reduced L-type calcium current (ICa) amplitude.
- Lower protein levels of the L-type calcium channel alpha-subunit and decreased rates of ICa inactivation were observed.
- Sarcoplasmic reticulum (SR) calcium content decreased significantly, associated with reduced SERCA2 and calsequestrin-2 protein levels, while spontaneous SR calcium release remained unaffected.
Conclusions:
- Aging is associated with diminished SR calcium content, L-type calcium current, and calcium transient amplitude in human atrial myocytes.
- These age-related alterations may contribute to a progressive decline in right atrial contractile function.
- The findings highlight critical changes in cardiac calcium handling with advancing age.
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.
