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

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.

Molecular basis of funny current (If) in normal and failing human heart.

I(f) overexpression has been functionally demonstrated in ventricular myocytes from failing human hearts. Altered expression of I(f)-channels as a consequence of electrophysiological remodeling may represent an arrhythmogenic mechanism in heart failure; however, the molecular basis of I(f) overexpression in human cardiac disease is unknown. HCN1, 2 and 4 subtypes, which encode I(f)-channels, have been identified in the heart.

Sinus node dysfunction and hyperpolarization-activated (HCN) channel subunit remodeling in a canine heart failure model.

Background: The hyperpolarization-activated cation current I(f) contributes significantly to sinoatrial node pacemaker function and possibly to ectopic arrhythmogenesis. Little is known about the expression of corresponding hyperpolarization-activated cyclic nucleotide-gated (HCN) channel subunits in normal hearts and HCN remodeling by diseases, like congestive heart failure (CHF), associated with disturbances of cardiac rhythm.

Methods And Results: We assessed expression of HCN1, 2 and 4 in normal mongrel dogs and dogs subjected to 2-week ventricular tachypacing-induced CHF.

Pharmacological modulation of the hyperpolarization-activated current (I f) in human atrial myocytes: focus on G protein-coupled receptors.

Aims: In human atrial myocytes (HuAM) two beta-adrenergic receptors (beta-AR) and four splicing-variants of the serotonin 5-HT(4) receptor are present. Multiple coupling with G stimulatory (G(s)) and G inhibitory (G(i)) proteins has been proposed for both beta(2)-AR and 5-HT((4b)) subtypes, but no functional data exist in HuAM. Serotonin (5-HT) and catecholamines are able to trigger arrhythmias in human atrium, but the underlying cellular mechanisms are not completely understood.

Atrial natriuretic peptide modulates the hyperpolarization-activated current (If) in human atrial myocytes.

Objectives: The relationship between atrial stretching and changes in cell excitability is well documented. Once stretched, human atrial myocytes (HuAM) release atrial natriuretic peptide (hANP). Receptors for hANP (NPR) are coupled to a guanylyl cyclase (GC) activity, and are present on HuAM, but the electrophysiological effects of hANP are largely unknown.

Restoration of cardiomyocyte functional properties by angiotensin II receptor blockade in diabetic rats.

Recent evidence suggests that blockade of the renin-angiotensin system ameliorates diabetes-induced cardiac dysfunction, but the mechanisms involved in this process remain elusive. We investigated the effect of treatment with an angiotensin II receptor blocker, losartan, on the metabolic and electrophysiological properties of cardiomyocytes isolated from streptozotocin-induced diabetic (STZ) rats. Glucose uptake and electrophysiological properties were measured in ventricular cardiomyocytes from normoglycemic and STZ-induced diabetic rats given vehicle or 20 mg x kg(-1) x day(-1) losartan for 8 weeks.

Prenatal exposure to carbon monoxide affects postnatal cellular electrophysiological maturation of the rat heart: a potential substrate for arrhythmogenesis in infancy.

Background: Maternal smoking is an independent risk factor for sudden infant death syndrome (SIDS). Carbon monoxide (CO) is a major component of smoke. No information is available about the effect of CO and/or smoking on postnatal maturation of the heart.

Treatment with irbesartan counteracts the functional remodeling of ventricular myocytes from hypertensive rats.

Changes in electrophysiological (action potential prolongation, decrease in transient outward current I(to), occurrence of the hyperpolarization-activated current I(f)) and contractile properties develop in hypertrophied ventricular myocytes, likely implicated in the increased propensity to arrhythmias. Angiotensin II is a key signal for myocyte hypertrophy; the effect of 8-week treatment with irbesartan, a type 1 angiotensin II receptor (AT(1)) antagonist, on cardiac remodeling was tested. Sixteen-month-old hypertensive rats (SHRs) were treated with irbesartan (20 mg/kg/d) or saline for 8 weeks.

Does recombinant human interleukin-11 exert direct electrophysiologic effects on single human atrial myocytes?

Recombinant human interleukin-11 (rhIL-11) treatment given to alleviate side effects of cancer therapy is associated with an increased susceptibility to atrial arrhythmias in elderly patients. To elucidate the mechanism underlying this action, we investigated the direct electrophysiologic effect of rhIL-11 on single human atrial myocytes (HuAM) using the patch-clamp technique. Action potentials (AP) at different driving rates were recorded in the perforated-patch configuration, and L-type calcium current (I(Ca,L)), outward potassium currents (I(to) and I(K)), and the hyperpolarization-activated pacemaker current If were measured in the disrupted whole-cell configuration.