title: Chronic atrial fibrillation alters the functional properties of If in the human atrium.
abstract: BACKGROUND
  Despite the evidence that the hyperpolarization-activated current (If) is highly modulated in human cardiomyopathies, no definite data exist in chronic atrial fibrillation (cAF). We investigated the expression, function, and modulation of If in human cAF.
  
  
  RESULTS
  Right atrial samples were obtained from sinus rhythm (SR, n = 49) or cAF (duration >1 year, n = 31) patients undergoing corrective cardiac surgery. Among f-channel isoforms expressed in the human atrium (HCN1, 2 and 4), HCN4 mRNA levels measured by RT-PCR were significantly reduced. However, protein expression was preserved in cAF compared to SR (+85% for HCN4); concurrently, miR-1 expression was significantly reduced. In patch-clamped atrial myocytes, current-specific conductance (gf) was significantly increased in cAF at voltages around the threshold for If activation (-60 to -80 mV); accordingly, a 10-mV rightward shift of the activation curve occurred (P < 0.01). β-Adrenergic and 5-HT4 receptor stimulation exerted similar effects on If in cAF and SR cells, while the ANP-mediated effect was significantly reduced (P < 0.02), suggesting downregulation of natriuretic peptide signaling.
  
  
  CONCLUSIONS
  In human cAF modifications in transcriptional and posttranscriptional mechanisms of HCN channels occur, associated with a slight yet significant gain-of-function of If , which may contribute to enhanced atrial ectopy.
authors.affiliation: Center for Molecular Medicine (C.I.M.M.B.A.), Department NEUROFARBA, University of Firenze, Florence, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Stillitano
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lonardo
authors.forename: Gabriele
authors.initials: G
authors.lastname: Giunti
authors.forename: Martina
authors.initials: M
authors.lastname: Del Lungo
authors.forename: Raffaele
authors.initials: R
authors.lastname: Coppini
authors.forename: Valentina
authors.initials: V
authors.lastname: Spinelli
authors.forename: Laura
authors.initials: L
authors.lastname: Sartiani
authors.forename: Corrado
authors.initials: C
authors.lastname: Poggesi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mugelli
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Cerbai
mesh_terms: D000200:Action Potentials; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001281:Atrial Fibrillation / Q000235:genetics / Q000378:metabolism*; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D002908:Chronic Disease; D005260:Female; D006325:Heart Atria / Q000378:metabolism; D006801:Humans; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000235:genetics / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000378:metabolism; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism; D058828:Serotonin 5-HT4 Receptor Agonists / Q000494:pharmacology; D014158:Transcription, Genetic
chemical_list: D000318:Adrenergic beta-Agonists; C578665:HCN1 protein, human; C578710:HCN2 protein, human; C119587:HCN4 protein, human; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; C544547:MIRN1 microRNA, human; D035683:MicroRNAs; D009124:Muscle Proteins; D015221:Potassium Channels; D012333:RNA, Messenger; D058828:Serotonin 5-HT4 Receptor Agonists; D009320:Atrial Natriuretic Factor
keywords: If; atrial fibrillation; atrial natriuretic peptide; hyperpolarization-activated cyclic nucleotide gated channels; serotonin; valvular heart disease; β-adrenergic stimulation