title: Changes in ion channel gene expression underlying heart failure-induced sinoatrial node dysfunction.
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.
  
  
  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.affiliation: University of Manchester, Manchester, UK.
authors.forename: Joseph
authors.initials: J
authors.lastname: Yanni
authors.forename: James O
authors.initials: JO
authors.lastname: Tellez
authors.forename: Michal
authors.initials: M
authors.lastname: Maczewski
authors.forename: Urszula
authors.initials: U
authors.lastname: Mackiewicz
authors.forename: Andrzej
authors.initials: A
authors.lastname: Beresewicz
authors.forename: Rudi
authors.initials: R
authors.lastname: Billeter
authors.forename: Halina
authors.initials: H
authors.lastname: Dobrzynski
authors.forename: M R
authors.initials: MR
authors.lastname: Boyett
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000235:genetics / Q000502:physiology; D017630:Connexins / Q000235:genetics / Q000502:physiology; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D006325:Heart Atria / Q000473:pathology / Q000503:physiopathology; D006333:Heart Failure / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D006339:Heart Rate / Q000502:physiology; D007473:Ion Channels / Q000235:genetics* / Q000502:physiology*; D008297:Male; D009203:Myocardial Infarction / Q000235:genetics / Q000503:physiopathology; D018995:Myosin Heavy Chains / Q000235:genetics / Q000502:physiology; D015221:Potassium Channels / Q000235:genetics / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012849:Sinoatrial Node / Q000503:physiopathology*; D015222:Sodium Channels / Q000235:genetics / Q000502:physiology; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000502:physiology
chemical_list: D015220:Calcium Channels; D017630:Connexins; D007473:Ion Channels; C000594638:MYH7 protein, rat; D015221:Potassium Channels; C452850:Slc9a1 protein, rat; D015222:Sodium Channels; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; D018995:Myosin Heavy Chains