INTRODUCTION: 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. METHODS AND 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.

Chronic Atrial Fibrillation Alters the Functional Properties of Ifin the Human Atrium / Francesca, Stillitano; Giuseppe, Lonardo; Gabriele, Giunti; Martina Del, Lungo; Raffaele, Coppini; Valentina, Spinelli; Laura, Sartiani; Corrado, Poggesi; Alessandro, Mugelli; Elisabetta, Cerbai. - In: JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY. - ISSN 1045-3873. - ELETTRONICO. - 24:(2013), pp. 1391-1400. [10.1111/jce.12212]

Chronic Atrial Fibrillation Alters the Functional Properties of Ifin the Human Atrium

DEL LUNGO, MARTINA;COPPINI, RAFFAELE;SPINELLI, VALENTINA;SARTIANI, LAURA;POGGESI, CORRADO;MUGELLI, ALESSANDRO;CERBAI, ELISABETTA
2013

Abstract

INTRODUCTION: 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. METHODS AND 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.
2013
24
1391
1400
Francesca, Stillitano; Giuseppe, Lonardo; Gabriele, Giunti; Martina Del, Lungo; Raffaele, Coppini; Valentina, Spinelli; Laura, Sartiani; Corrado, Poggesi; Alessandro, Mugelli; Elisabetta, Cerbai
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/817539
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