Pitx2c deficiency confers cellular electrophysiological hallmarks of atrial fibrillation to isolated atrial myocytes - 29/04/23
Abstract |
Aims |
Atrial fibrillation (AF) has been associated with altered expression of the transcription factor Pitx2c and a high incidence of calcium release-induced afterdepolarizations. However, the relationship between Pitx2c expression and defective calcium homeostasis remains unclear and we here aimed to determine how Pitx2c expression affects calcium release from the sarcoplasmic reticulum (SR) and its impact on electrical activity in isolated atrial myocytes.
Methods |
To address this issue, we applied confocal calcium imaging and patch-clamp techniques to atrial myocytes isolated from a mouse model with conditional atrial-specific deletion of Pitx2c.
Results |
Our findings demonstrate that heterozygous deletion of Pitx2c doubles the calcium spark frequency, increases the frequency of sparks/site 1.5-fold, the calcium spark decay constant from 36 to 42 ms and the wave frequency from none to 3.2 min−1. Additionally, the cell capacitance increased by 30% and both the SR calcium load and the transient inward current (ITI) frequency were doubled. Furthermore, the fraction of cells with spontaneous action potentials increased from none to 44%. These effects of Pitx2c deficiency were comparable in right and left atrial myocytes, and homozygous deletion of Pitx2c did not induce any further effects on sparks, SR calcium load, ITI frequency or spontaneous action potentials.
Conclusion |
Our findings demonstrate that heterozygous Pitx2c deletion induces defects in calcium homeostasis and electrical activity that mimic derangements observed in right atrial myocytes from patients with AF and suggest that Pitx2c deficiency confers cellular electrophysiological hallmarks of AF to isolated atrial myocytes.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | Atrial specific Pitx2c deletion promotes Ca2+ release-induced afterdepolarizations. |
• | Pitx2c deletion increases cell surface area but reduces L-type Ca2+ current density. |
• | Changes are similar in isolated right and left atrial myocytes. |
• | The alterations mimic derangements observed in atrial fibrillation. |
Keywords : Pitx2c deficiency, Mouse atrial myocytes, Sarcoplasmic reticulum, Calcium sparks, Afterdepolarizations
Plan
Vol 162
Article 114577- juin 2023 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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