The HCN4 Channel Mutation D553N Associated With Bradycardia Has a C-linker Mediated Gating Defect
نویسندگان
چکیده
منابع مشابه
The HCN4 channel mutation D553N associated with bradycardia has a C-linker mediated gating defect.
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...
متن کاملUeda et al, Trafficking-defective HCN4 mutation in cardiac arrhythmia - 1 - Functional characterization of a trafficking-defective HCN4 mutation, D553N, associated with cardiac arrhythmia Running title: Trafficking-defective HCN4 mutation in cardiac arrhythmia
1 Functional characterization of a trafficking-defective HCN4 mutation, D553N, associated with cardiac arrhythmia Running title: Trafficking-defective HCN4 mutation in cardiac arrhythmia Kazuo Ueda, Kazufumi Nakamura, Takeharu Hayashi, Natsuko Inagaki, Megumi Takahashi, Takuro Arimura, Hiroshi Morita, Yasushi Higashiuesato, Yuji Hirano, Michio Yasunami, Shuichi Takishita, Akira Yamashina, Tohru...
متن کاملCyclic dinucleotides bind the C-linker of HCN4 to control channel cAMP responsiveness.
cAMP mediates autonomic regulation of heart rate by means of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which underlie the pacemaker current If. cAMP binding to the C-terminal cyclic nucleotide binding domain enhances HCN open probability through a conformational change that reaches the pore via the C-linker. Using structural and functional analysis, we identified a bin...
متن کاملFamilial sinus bradycardia associated with a mutation in the cardiac pacemaker channel.
We found that sinus bradycardia in members of a large family was associated with a mutation in the gene coding for the pacemaker HCN4 ion channel. Pacemaker channels of the sinoatrial node generate spontaneous activity and mediate cyclic AMP (cAMP)-dependent autonomic modulation of the heart rate. The mutation associated with bradycardia is located near the cAMP-binding site; functional analysi...
متن کاملPoint mutation in the HCN4 cardiac ion channel pore affecting synthesis, trafficking, and functional expression is associated with familial asymptomatic sinus bradycardia.
BACKGROUND The hyperpolarization-activated nucleotide-gated channel--HCN4 plays a major role in the diastolic depolarization of sinus atrial node cells. Mutant HCN4 channels have been found to be associated with inherited sinus bradycardia. METHODS AND RESULTS Sixteen members of a family with sinus bradycardia were evaluated. Evaluation included a clinical questionnaire, 12-lead ECGs, Holter ...
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ژورنال
عنوان ژورنال: Cellular Physiology and Biochemistry
سال: 2012
ISSN: 1421-9778,1015-8987
DOI: 10.1159/000343314