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Estimating Bilateral Atrial Function by Cardiovascular Magnetic Resonance Feature Tracking in Patients with Paroxysmal Atrial Fibrillation
08:10

Estimating Bilateral Atrial Function by Cardiovascular Magnetic Resonance Feature Tracking in Patients with Paroxysmal Atrial Fibrillation

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Chronic atrial fibrillation alters the functional properties of If in the human atrium

Francesca Stillitano1, Giuseppe Lonardo, Gabriele Giunti

  • 1Center for Molecular Medicine (C.I.M.M.B.A.), Department NEUROFARBA, University of Firenze, Florence, Italy.

Journal of Cardiovascular Electrophysiology
|July 23, 2013
PubMed

Insights

In chronic atrial fibrillation (cAF), HCN channel expression and function are altered. These changes lead to a gain-of-function in the hyperpolarization-activated current (If), potentially increasing atrial ectopy.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Electrophysiology

Background:

  • The hyperpolarization-activated current (If) is crucial in cardiac function but its role in chronic atrial fibrillation (cAF) remains unclear.
  • Previous studies show If modulation in cardiomyopathies, yet data in human cAF are lacking.

Purpose of the Study:

  • To investigate the expression, function, and modulation of the If current in human cAF.
  • To elucidate the underlying molecular mechanisms of If changes in cAF.

Main Methods:

  • Analysis of right atrial samples from sinus rhythm (SR) and cAF patients.
  • Quantitative RT-PCR for HCN channel mRNA levels.
  • Western blotting for protein expression.
  • Patch-clamp electrophysiology to measure If in atrial myocytes.
  • Assessment of receptor-mediated modulation of If.

Main Results:

  • HCN4 mRNA levels were reduced in cAF, but HCN4 protein expression was significantly increased (+85%).
  • miR-1 expression was significantly reduced in cAF.
  • Atrial myocytes from cAF patients showed increased If conductance and a rightward shift in activation curves.
  • Natriuretic peptide signaling was downregulated in cAF.

Conclusions:

  • Human cAF involves altered transcriptional and posttranscriptional regulation of HCN channels.
  • These modifications result in a functional gain-of-function for the If current.
  • The enhanced If current may contribute to increased atrial ectopy in cAF.
Abstract

Keywords:
Ifatrial fibrillationatrial natriuretic peptidehyperpolarization-activated cyclic nucleotide gated channelsserotoninvalvular heart diseaseβ-adrenergic stimulation

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