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

Abstract

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.

Thyroid‐stimulating hormone regulates cardiac function through modulating HCN2 via targeting microRNA ‐1a

“…[28][29][30][31] Cardiac HCN2 plays an important role in the electrical remodeling of cardiac hypertrophy and increases the risk of arrhythmia. [32][33][34][35] HCN2 is considered to be the molecular propagators of the ventricular If. 8 The If current is a mixed K + /Na + depolarizing inward current, which contributes to the depolarization of cardiac F I G U R E 4 TSH affects the expression of miR-1a and HCN2 in vitro.…”

“…Recent studies revealed that the expression of HCN2 in cardiomyocytes under pathological conditions (such as end‐stage heart failure, hypertrophic cardiomyopathy, and acute myocardial infarction) was significantly increased 28–31 . Cardiac HCN2 plays an important role in the electrical remodeling of cardiac hypertrophy and increases the risk of arrhythmia 32–35 . HCN2 is considered to be the molecular propagators of the ventricular If 8 .…”

“…36 Under a variety pathophysiological factors such as ventricular hypertrophy and heart failure, the abnormal expression of myocardial HCN2 leads to abnormal If currents, leading to various cardiac dysfunctions. 8,35,36 In addition, calcium ion-mediated myocardial contraction coupling is the initial link of myocardial contraction and relaxation. Abnormal expression of calcium-related channels can induce an imbalance of calcium homeostasis, which in turn leads to cardiomyocyte contractile dysfunction.…”

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

“…AF is a pathological condition in which ionic current remodeling has been demonstrated [14] . Regarding If current, an association between HCN overexpression in atrial and pulmonary vein cardiomyocytes and presence of AF has been reported in animal models and human [15][16][17][18] . In a canine model, He et al [17] demonstrated that mRNA and protein expression levels of HCN2 and HCN4 in the AF group were significantly increased when compared with the control group.…”

“…Regarding If current, an association between HCN overexpression in atrial and pulmonary vein cardiomyocytes and presence of AF has been reported in animal models and human [15][16][17][18] . In a canine model, He et al [17] demonstrated that mRNA and protein expression levels of HCN2 and HCN4 in the AF group were significantly increased when compared with the control group. Li et al [18] analyzed right atrial appendage samples collected from 60 patients undergoing coronary artery bypass grafting; they observed that mRNA and protein expression levels of HCN2 and HCN4 channels in the right atrial appendage increased with age.…”