Changes in Ion channel gene expression underlying heart failure-induced sinoatrial node dysfunction

Joseph Yanni Gerges, Joseph Yanni, James O. Tellez, Michal Ma̧cZewski, Urszula MacKiewicz, Andrzej Beresewicz, Rudi Billeter, Halina Dobrzynski, M. R. Boyett, Michal Maczewski

    Research output: Contribution to journalArticlepeer-review

    Abstract

    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, KvLQT1, Kir2.4, 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; Ca2+-, Na+-, and H+-handling proteins; and receptors in the SAN. (Circ Heart Fail. 2011;4:496-508.). © 2011 American Heart Association, Inc.
    Original languageEnglish
    Pages (from-to)496-508
    Number of pages12
    JournalCirculation: Heart Failure
    Volume4
    Issue number4
    DOIs
    Publication statusPublished - Jul 2011

    Keywords

    • Heart failure
    • Ion channels
    • Sinoatrial node

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