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Updated: Mar 16, 2026
Isolation of Atrial Myocytes from Adult Mice
Published on: July 25, 2019
Evidence for a functional role of calsequestrin 2 in mouse atrium
U Gergs1, C M Fahrion1, P Bock1
1Institut für Pharmakologie und Toxikologie, Medizinische Fakultät, Martin-Luther-Universität Halle-Wittenberg, Halle/Saale, Germany.
Aim:
Several genetically modified mice models were studied so far to investigate the role of cardiac calsequestrin (CSQ2) for the contractile function of the ventricle and for the occurrence of ventricular tachycardia. Using a CSQ2 knockout mouse, we wanted to study also the atrial function of CSQ2.
Methods:
The influence of CSQ2 on atrial function and, for comparison, ventricular function was studied in isolated cardiac preparations and by echocardiography as well as electrocardiography in mice with deletion of CSQ2.
Results:
Using deletion of exon 1, we have successfully generated a constitutive knockout mouse of the calsequestrin 2 gene (CSQ2-/- ). CSQ2 protein was absent in the heart (atrium, ventricle), but also in oesophagus and skeletal muscle of homozygous knockout mice. In 6-month-old CSQ2-/- mice, relative left atrial weight was increased, whereas relative heart weight was unchanged. The staircase phenomena in paced left atrial preparations on force of contraction and the post-rest potentiation were different between wild type and CSQ2-/- indicative for a decreased sarcoplasmic Ca2+ load and supporting an important role of CSQ2 also in the atrium. The incidence of arrhythmias was increased in CSQ2-/- . In 2-year-old CSQ2-/- mice, cardiac hypertrophy and heart failure were noted possibly as a result of chronically increased cytosolic Ca2+ levels.
Conclusion:
These data suggest a functional role of CSQ2 not only in the ventricle but also in the atrium of mammalian hearts. Loss of CSQ2 function can cause not only arrhythmias, but also cardiac hypertrophy and heart failure.
Insights
Cardiac calsequestrin (CSQ2) plays a vital role in both atrial and ventricular function. Loss of CSQ2 in mice leads to arrhythmias, cardiac hypertrophy, and heart failure, highlighting its importance in maintaining heart health.
Area of Science:
- Cardiology
- Molecular Biology
- Physiology
Background:
- Cardiac calsequestrin (CSQ2) is crucial for ventricular function and arrhythmia development.
- Previous studies focused on CSQ2's role in the ventricle, leaving atrial function less explored.
Purpose of the Study:
- To investigate the functional role of CSQ2 in atrial function.
- To compare atrial and ventricular function in CSQ2 knockout mice.
Main Methods:
- Generation of a constitutive CSQ2 knockout mouse model (CSQ2-/-).
- Assessment of cardiac function using isolated atrial preparations, echocardiography, and electrocardiography.
- Analysis of cardiac structure and incidence of arrhythmias.
Main Results:
- CSQ2 protein was absent in knockout mice hearts, esophagus, and skeletal muscle.
- CSQ2-/- mice exhibited altered atrial contractility and increased incidence of arrhythmias.
- Older CSQ2-/- mice developed cardiac hypertrophy and heart failure, linked to altered calcium handling.
Conclusions:
- CSQ2 is functionally important in both atrial and ventricular mammalian heart tissue.
- Disruption of CSQ2 function can precipitate arrhythmias, cardiac hypertrophy, and heart failure.
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