BACKGROUND: Heart failure (HF) causes a decline in the function of the pacemaker of the heart-the sinoatrial node (SAN). The aim of the study was to investigate HF-induced changes in the expression of the ion channels and related proteins underlying the pacemaker activity of the SAN. METHODS AND RESULTS: HF was induced in rats by the ligation of the proximal left coronary artery. HF animals showed an increase in the left ventricular (LV) diastolic pressure (317%) and a decrease in the LV systolic pressure (19%) compared with sham-operated animals. They also showed SAN dysfunction wherein the intrinsic heart rate was reduced (16%) and the corrected SAN recovery time was increased (56%). Quantitative polymerase chain reaction was used to measure gene expression. Of the 91 genes studied during HF, 58% changed in the SAN, although only 1% changed in the atrial muscle. For example, there was an increase in the expression of ERG, K(v)LQT1, K(ir)2.4, TASK1, TWIK1, TWIK2, calsequestrin 2, and the A1 adenosine receptor in the SAN that could explain the slowing of the intrinsic heart rate. In addition, there was an increase in Na(+)-H(+) exchanger, and this could be the stimulus for the remodeling of the SAN. CONCLUSIONS: SAN dysfunction is associated with HF and is the result of an extensive remodeling of ion channels; gap junction channels; Ca(2+)-, Na(+)-, and H(+)-handling proteins; and receptors in the SAN.
BACKGROUND:Heart failure (HF) causes a decline in the function of the pacemaker of the heart-the sinoatrial node (SAN). The aim of the study was to investigate HF-induced changes in the expression of the ion channels and related proteins underlying the pacemaker activity of the SAN. METHODS AND RESULTS: HF was induced in rats by the ligation of the proximal left coronary artery. HF animals showed an increase in the left ventricular (LV) diastolic pressure (317%) and a decrease in the LV systolic pressure (19%) compared with sham-operated animals. They also showed SAN dysfunction wherein the intrinsic heart rate was reduced (16%) and the corrected SAN recovery time was increased (56%). Quantitative polymerase chain reaction was used to measure gene expression. Of the 91 genes studied during HF, 58% changed in the SAN, although only 1% changed in the atrial muscle. For example, there was an increase in the expression of ERG, K(v)LQT1, K(ir)2.4, TASK1, TWIK1, TWIK2, calsequestrin 2, and the A1 adenosine receptor in the SAN that could explain the slowing of the intrinsic heart rate. In addition, there was an increase in Na(+)-H(+) exchanger, and this could be the stimulus for the remodeling of the SAN. CONCLUSIONS: SAN dysfunction is associated with HF and is the result of an extensive remodeling of ion channels; gap junction channels; Ca(2+)-, Na(+)-, and H(+)-handling proteins; and receptors in the SAN.
Authors: Marcelo H A Ichige; Carla R Santos; Camila P Jordão; Alexandre Ceroni; Carlos E Negrão; Lisete C Michelini Journal: J Physiol Date: 2016-08-29 Impact factor: 5.182
Authors: Qing Lou; Brian J Hansen; Olga Fedorenko; Thomas A Csepe; Anuradha Kalyanasundaram; Ning Li; Lori T Hage; Alexey V Glukhov; George E Billman; Raul Weiss; Peter J Mohler; Sándor Györke; Brandon J Biesiadecki; Cynthia A Carnes; Vadim V Fedorov Journal: Circulation Date: 2014-05-16 Impact factor: 29.690
Authors: Ian P Temple; Sunil Jit R J Logantha; Mais Absi; Yu Zhang; Eleftheria Pervolaraki; Joseph Yanni; Andrew Atkinson; Maria Petkova; Gillian M Quigley; Simon Castro; Mark Drinkhill; Heiko Schneider; Oliver Monfredi; Elizabeth Cartwright; Min Zi; Tomoko T Yamanushi; Vaikom S Mahadevan; Alison M Gurney; Ed White; Henggui Zhang; George Hart; Mark R Boyett; Halina Dobrzynski Journal: Circ Arrhythm Electrophysiol Date: 2016-12