Emerging evidence has shown that aldosterone blockers reduced the incidence of ventricular arrhythmias in patients with myocardial infarction (MI). However, the mechanism remains unknown. In this study, we investigated the mechanism by which spironolactone, a classic aldosterone blocker, regulates hyperpolarization-activated cyclic nucleotide-gated channel (HCN) protein expression in ischemic r...

BACKGROUND The pacemaker current I(f) is present in atrial and ventricular myocytes. However, it remains controversial whether I(f) overexpression in diseased states might play a role for arrhythmogenesis, because first I(f) activation in whole-cell recordings hardly overlapped the diastolic voltage of working myocardium. METHODS AND RESULTS To obtain further insight into I(HCN) and I(f) prop...

Background—The pacemaker current If is present in atrial and ventricular myocytes. However, it remains controversial whether If overexpression in diseased states might play a role for arrhythmogenesis, because first If activation in whole-cell recordings hardly overlapped the diastolic voltage of working myocardium. Methods and Results—To obtain further insight into IHCN and If properties, we p...

BACKGROUND The pacemaker current I(f) contributes to spontaneous diastolic depolarization of cardiac autonomic cells. In heterologous expression, HCN channels exhibit a hyperpolarization-activated inward current similar to I(f). However, the links between HCN genes and native I(f) are largely inferential, and it remains unknown whether I(f) is essential for cardiac pacing. METHODS AND RESULTS...

Hyperpolarization-activated cyclic nucleotide-gated (HCN) cation channels mediate pacemaker currents in the atrium. The microRNA (miR) families miR-1 and miR-133 regulate the expression of multiple genes involved in myocardial function, including HCN channels. It was hypothesized that age‑dependent changes in HCN2, HCN4, miR‑1 and miR‑133 expression may contribute to age‑associated atrial fibri...

The sinoatrial node (SAN) is composed mostly of pacemaker, transitional and Purkinje-like cells. Pacemaker cells, especially in the centre of the SAN, are surrounded by dense fibrous tissue and do not have any contact with transitional cells. We hypothesize that the SAN contains telocytes that have contacts with pacemaker cells and contractile myocardium. Immunohistochemistry using antibodies a...

BACKGROUND/AIMS The D553N mutation located in the C-linker of the cardiac pacemaker channel HCN4 is thought to cause sino-atrial dysfunction via a pronounced dominant-negative trafficking defect. Since HCN4 mutations usually have a minor defect in channel gating, it was our aim to further characterize the disease causing mechanism of D553N. METHODS Fluorescence microscopy, FACS, TEVC and patc...

OBJECTIVE To reveal the structural characteristics of the sinoatrial node (SAN) and the distribution of hyperpolarization-activated cyclic nucleotide-gated cation channels (HCN) in the SAN in the mouse. METHODS The structure of the SAN and the distribution of HCN channels in the SAN in the mouse were studied by histology and immunolabelling of ANP, Cx43 and HCN channels. RESULTS The mouse S...