Pitx2c deficiency confers cellular electrophysiological hallmarks of atrial fibrillation to isolated atrial myocytes
Tarifa, Carmen (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Serra, Selma A. (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Herraiz-Martínez, Adela (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Lozano-Velasco, Estefanía (Universidad de Jaén)
Benítez, Raúl (Universitat Politècnica de Catalunya)
Aránega, Amelia (Universidad de Jaén)
Franco, Diego (Univesidad de Jaén)
Hove-Madsen, Leif (Institut d'Investigació Biomèdica Sant Pau)
Universitat Autònoma de Barcelona

Data:	2023
Resum:	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. 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. 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. Additionally, the cell capacitance increased by 30% and both the SR calcium load and the transient inward current (I) 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, I frequency or spontaneous action potentials. 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.
Ajuts:	Agencia Estatal de Investigación PID2020-116927RB-C21 Agencia Estatal de Investigación PID2020-116927RB-C22
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Afterdepolarizations ; Calcium sparks ; Mouse atrial myocytes ; Pitx2c deficiency ; Sarcoplasmic reticulum
Publicat a:	Biomedicine & pharmacotherapy, Vol. 162 (june 2023) , p. 114577, ISSN 1950-6007

DOI: 10.1016/j.biopha.2023.114577
PMID: 37001181

10 p, 4.1 MB

El registre apareix a les col·leccions:
Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut de Recerca Sant Pau
Articles > Articles de recerca
Articles > Articles publicats