Evidence for a functional role of calsequestrin 2 in mouse atrium

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.