Cohesin-protein Shugoshin-1 controls cardiac automaticity via HCN4 pacemaker channel
نویسندگان
چکیده
منابع مشابه
The cardiac pacemaker-specific channel Hcn4 is a direct transcriptional target of MEF2.
AIMS Hcn4, which encodes the hyperpolarization-activated, cyclic nucleotide-sensitive channel (I(h)), is a well-established marker of the cardiac sino-atrial node. We aimed to identify cis-elements in the genomic locus of the Hcn4 gene that regulate the transcription of Hcn4. METHODS AND RESULTS We screened evolutionarily conserved non-coding sequences (CNSs) that are often involved in the re...
متن کاملDeep bradycardia and heart block caused by inducible cardiac-specific knockout of the pacemaker channel gene Hcn4.
Cardiac pacemaking generation and modulation rely on the coordinated activity of several processes. Although a wealth of evidence indicates a relevant role of the I(f) ("funny," or pacemaker) current, whose molecular constituents are the hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels and particularly HCN4, work with mice where Hcn genes were knocked out, or functionally mod...
متن کاملIon channel-kinase TRPM7 is required for maintaining cardiac automaticity.
Sick sinus syndrome and atrioventricular block are common clinical problems, often necessitating permanent pacemaker placement, yet the pathophysiology of these conditions remains poorly understood. Here we show that Transient Receptor Potential Melastatin 7 (TRPM7), a divalent-permeant channel-kinase of unknown function, is highly expressed in embryonic myocardium and sinoatrial node (SAN) and...
متن کاملProteolytic processing of HCN2 and co-assembly with HCN4 in the generation of cardiac pacemaker channels.
In sino-atrial and atrio-ventricular nodal cells, hyperpolarization-activated cyclic nucleotide-gated (HCN) inward current carrying cationic channels, I(f), are expressed that contribute importantly to the diastolic depolarization critical for cardiac pacemaker activity. Although previous studies have demonstrated myocardial expression of both the HCN2 and HCN4 subunits, the specific roles of t...
متن کاملSrc tyrosine kinase alters gating of hyperpolarization-activated HCN4 pacemaker channel through Tyr531.
We recently discovered that the constitutively active Src tyrosine kinase can enhance hyperpolarization-activated, cyclic nucleotide-gated (HCN) 4 channel activity by binding to the channel protein. To investigate the mechanism of modulation by Src of HCN channels, we studied the effects of a selective inhibitor of Src tyrosine kinase, 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimi...
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ژورنال
عنوان ژورنال: Nature Communications
سال: 2021
ISSN: 2041-1723
DOI: 10.1038/s41467-021-22737-5