in left human atrium: a potential contributor to atrial ectopy

Zorn-Pauly, Klaus; Schäffer, Péter; Pelzmann, Brigitte; Lang, Petra; Mächler, Heinrich; Rigler, B; Koidl, Bernd

doi:10.1016/j.cardiores.2004.07.001

Cited by 39 publications

(28 citation statements)

References 29 publications

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“…In contrast, the activation threshold of the I h of diseased cardiomyocytes is usually not shifted to more positive values compared with normal ventricular I h (76,139,177,182). Increased I h densities strongly raise the tendency of the ventricular muscle to develop ectopic, "pacemaker-like" action potentials and, thereby, contribute to arrhythmia and to sudden death (72,73,139,182,374,452).…”

Section: Cardiac Remodeling and Arrhythmiamentioning

confidence: 98%

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Hyperpolarization-Activated Cation Channels: From Genes to Function

Biel

Wahl‐Schott²,

Michalakis³

et al. 2009

Physiological Reviews

872

974

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Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels comprise a small subfamily of proteins within the superfamily of pore-loop cation channels. In mammals, the HCN channel family comprises four members (HCN1-4) that are expressed in heart and nervous system. The current produced by HCN channels has been known as Ih (or If or Iq). Ih has also been designated as pacemaker current, because it plays a key role in controlling rhythmic activity of cardiac pacemaker cells and spontaneously firing neurons. Extensive studies over the last decade have provided convincing evidence that Ih is also involved in a number of basic physiological processes that are not directly associated with rhythmicity. Examples for these non-pacemaking functions of Ih are the determination of the resting membrane potential, dendritic integration, synaptic transmission, and learning. In this review we summarize recent insights into the structure, function, and cellular regulation of HCN channels. We also discuss in detail the different aspects of HCN channel physiology in the heart and nervous system. To this end, evidence on the role of individual HCN channel types arising from the analysis of HCN knockout mouse models is discussed. Finally, we provide an overview of the impact of HCN channels on the pathogenesis of several diseases and discuss recent attempts to establish HCN channels as drug targets.

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Section: Cardiac Remodeling and Arrhythmiamentioning

confidence: 98%

“…Examination of mRNA levels in hypertrophied atrial and ventricular myocytes revealed an upregulation of HCN2 and HCN4 in different animal models (72,73,139,177,182,374,375,452). In addition, upregulation of HCN4 was found in human patients with end-stage heart failure (45).…”

Section: Cardiac Remodeling and Arrhythmiamentioning

confidence: 99%

Hyperpolarization-Activated Cation Channels: From Genes to Function

Biel

Wahl‐Schott²,

Michalakis³

et al. 2009

Physiological Reviews

872

974

View full text Add to dashboard Cite

show abstract

“…Further studies into this association are necessary in order to reveal the role played by HCN channels in cases of AF electrical remodeling. Zorn-Pauly et al (12) found that increases in the I f current may cause atrial myocytes to function in a similar manner to pacemaker cells, subsequently increasing the local atrial automaticity, decreasing …”

Section: Discussionmentioning

confidence: 99%

“…All the dogs were implanted with pacemakers in a subcutaneous neck pocket using a previously described procedure (12,13). Following a 24-h recovery period, seven dogs were subjected to continuous right atrial pacing at 400 bpm for 50 days (AF group).…”

Section: Animal Model Establishmentmentioning

confidence: 99%

Expression of hyperpolarization-activated cyclic nucleotide-gated channel isoforms in a canine model of atrial fibrillation

Zhang

Gan

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. The aim of the present study was to analyze the mRNA and protein expression levels of atrial hyperpolarization-activated cyclic nucleotide-gated (HCN) channel isoforms in the left atrial muscle of dogs with multiple organ failure. A total of 14 beagle dogs with multiple organ failure, including seven cases with sinus rhythm and seven cases with atrial fibrillation (AF), underwent surgery to remove a sample of left atrial appendage tissue. The expression levels of a number of HCN channel subtypes were subsequently measured using quantitative polymerase chain reaction and western blot analysis. The mRNA and protein expression levels of HCN2 and HCN4 increased significantly in the AF group when compared with the sinus rhythm group. However, expression of the HCN1 isoform was not detected. Therefore, increased expression levels of HCN2 and HCN4 may be important molecular mechanisms in the pathogenesis of AF, which were associated with differences in patients with valvular heart disease.

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“…However, the exact role of HCN channels in generating and sustaining atrial arrhythmias is not known. Zorn-Pauly et al [20] found that increases in the If current may cause atrial myocytes to function like pacemaker cells, subsequently increasing the local atrial automaticity, decreasing the effective atrial refractory period and enhancing the risk of atrial arrhythmias. Zicha et al [21] analyzed atrial myocytes in dogs with rapid ventricular pacemaker activity and demonstrated that If enhancement, and the associated HCN channel overexpression, contributed to heart failure-induced ventricular arrhythmias.…”

Section: Pacemaker Funny Current In Healthy Heart and Under Pathologimentioning

confidence: 99%

Heart Rate Control in Non-Paroxysmal Atrial Fibrillation. A New Indication for Ivabradine?

Caminiti

Cacciapuoti

Fossati

et al. 2017

Journal of Cardiology and Therapy

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stable angina and chronic heart failure in sinus rhythm. According to very preliminary data, ivabradine shows heart rate lowering proprieties in non-paroxysmal AF when used alone or in association to other heart rate lowering drugs. Interestingly, studies suggest that this seems to translate into clinical benefits such as improvement of exercise tolerance and ejection fraction. However, new trials are needed to confirm the effectiveness and safety of ivabradine in nonparoxysmal AF. INTRODUCTIONAtrial fibrillation (AF) is the most common cardiac arrhythmia and its incidence and prevalence increase with age. Although by itself it is a non-fatal arrhythmia, it is often associated with a considerable comorbidity and an increased risk of stroke and heart failure. Patients with AF have significantly poorer quality of life than healthy controls, experiencing a variety of symptoms including lethargy, palpitations, dyspnoea, chest tightness, sleeping difficulties, and psychosocial distress [1] . These symptoms are often related to an uncontrolled ventricular rate and they can be significantly improved by the administration of drugs aimed to establish heart rate (HR) control. In the setting of non-paroxysmal AF, rate-control is an integral part of the management of AF patients as underlined by the most recent guidelines [2] . In such patients, HR control is usually obtained by using drugs which prolong atrioventricular (AV) node refractoriness such as β-blockers, nondihydropyridine calcium channel blockers, and digoxin. These drugs can be used alone or in combination for resistant AF. In clinical practice the choice of drug and target HR depends on patient characteristics and comorbidities but the decision can be particularly challenging in elderly frail subjects with multiple comorbidities. Diltiazem and verapamil may have negative inotropic effects in patients ABSTRACTAtrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with poor quality of life and high rate of hospitalization in elderly frail patients. In patients with non-paroxysmal AF, optimizing heart rate is often the main goal but available drugs fail to reach heart rate control in about 30% of cases and this often happens because their doses can not be implemented due to side effects. Ivabradine is a pure heart rate lowering agent acting through the inhibition of If current in the sinus atrial cells, and it is widely used for patients with

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in left human atrium: a potential contributor to atrial ectopy

Cited by 39 publications

References 29 publications

Hyperpolarization-Activated Cation Channels: From Genes to Function

Hyperpolarization-Activated Cation Channels: From Genes to Function

Expression of hyperpolarization-activated cyclic nucleotide-gated channel isoforms in a canine model of atrial fibrillation

Heart Rate Control in Non-Paroxysmal Atrial Fibrillation. A New Indication for Ivabradine?

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