Triggered firing and atrial fibrillation in transgenic mice with selective atrial fibrosis induced by overexpression of TGF-ß1.
Circ J
; 76(6): 1354-62, 2012.
Article
en En
| MEDLINE
| ID: mdl-22447020
ABSTRACT
BACKGROUND:
Calcium transient triggered firing (CTTF) is induced by large intracellular calcium (Ca(i)) transient and short action potential duration (APD). We hypothesized that CTTF underlies the mechanisms of early afterdepolarization (EAD) and spontaneous recurrent atrial fibrillation (AF) in transgenic (Tx) mice with overexpression of transforming growth factor ß1 (TGF-ß1). METHODS ANDRESULTS:
MHC-TGFcys(33)ser Tx mice develop atrial fibrosis because of elevated levels of TGF-ß1. We studied membrane potential and Ca(i)transients of isolated superfused atria from Tx and wild-type (Wt) littermates. Short APD and persistently elevated Ca(i) transients promoted spontaneous repetitive EADs, triggered activity and spontaneous AF after cessation of burst pacing in Tx but not Wt atria (39% vs. 0%, P=0.008). We were able to map optically 4 episodes of spontaneous AF re-initiation. All first and second beats of spontaneous AF originated from the right atrium (4/4, 100%), which is more severely fibrotic than the left atrium. Ryanodine and thapsigargin inhibited spontaneous re-initiation of AF in all 7 Tx atria tested. Western blotting showed no significant changes of calsequestrin or sarco/endoplasmic reticulum Ca(2+)-ATPase 2a.CONCLUSIONS:
Spontaneous AF may occur in the Tx atrium because of CTTF, characterized by APD shortening, prolonged Ca(i) transient, EAD and triggered activity. Inhibition of Ca(2+) release from the sarcoplasmic reticulum suppressed spontaneous AF. Our results indicate that CTTF is an important arrhythmogenic mechanism in TGF-ß1 Tx atria.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fibrilación Atrial
/
Función Atrial
/
Señalización del Calcio
/
Factor de Crecimiento Transformador beta1
/
Sistema de Conducción Cardíaco
Límite:
Animals
Idioma:
En
Revista:
Circ J
Asunto de la revista:
ANGIOLOGIA
/
CARDIOLOGIA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos