Sick Sinus Syndrome 1, Autosomal Recessive

Last update 01 Nov 2024

Basic Info

Synonyms

SICK SINUS SYNDROME 1, SICK SINUS SYNDROME 1, AUTOSOMAL RECESSIVE, SICK SINUS SYNDROME, CONGENITAL

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Introduction-

100 Clinical Results associated with Sick Sinus Syndrome 1, Autosomal Recessive

100 Translational Medicine associated with Sick Sinus Syndrome 1, Autosomal Recessive

0 Patents (Medical) associated with Sick Sinus Syndrome 1, Autosomal Recessive

Literatures (Medical) associated with Sick Sinus Syndrome 1, Autosomal Recessive

13 Nov 2020·Polish Archives of Internal MedicineQ4 · MEDICINE

A novel <i>HCN4</i> variant related to familial sinus bradycardia, left ventricular noncompaction and thoracic aortic aneurysm

Q4 · MEDICINE

Article

Author: Bilińska, Zofia T ; Ponińska, Joanna ; Michalak, Ewa ; Śpiewak, Mateusz ; Płoski, Rafał ; Lutyńska, Anna

01 Mar 2018·The Journal of PhysiologyQ2 · MEDICINE

HCN4 pacemaker channels attenuate the parasympathetic response and stabilize the spontaneous firing of the sinoatrial node

Q2 · MEDICINE

Article

Author: Makita, Naomasa ; Kimoto, Hiroki ; Ushijima, Kazuo ; Ito, Masayuki ; Ishikawa, Taisuke ; Kozasa, Yuko ; Takano, Makoto ; Nakashima, Noriyuki

Key points

The contribution of HCN4 pacemaker channels in the autonomic regulation of the sino‐atrial node (SAN) has been a matter of debate.

The transgenic overexpression of HCN4 did not induce tachycardia, but reduced heart rate variability, while the conditional knockdown of HCN4 gave rise to sinus arrhythmia.

The response of the SAN to β‐adrenergic stimulation was not affected by overexpression or knockdown of HCN4 channels.

When HCN4 channels were knocked down, the parasympathetic response examined by cervical vagus nerve stimulation (CVNS) was enhanced; the CVNS induced complete sinus pause. The overexpression of HCN4 attenuated bradycardia induced by CVNS only during β‐adrenergic stimulation.

We concluded that HCN4 pacemaker channels stabilize the spontaneous firing by attenuating the parasympathetic response of the SAN.

AbstractThe heart rate is dynamically controlled by the sympathetic and parasympathetic nervous systems that regulate the sinoatrial node (SAN). HCN4 pacemaker channels are the well‐known causative molecule of congenital sick sinus syndrome. Although HCN4 channels are activated by cAMP, the sympathetic response of the SAN was preserved in patients carrying loss‐of‐function mutations of the HCN4 gene. In order to clarify the contribution of HCN4 channels in the autonomic regulation of the SAN, we developed novel gain‐of‐function mutant mice in which the expression level of HCN4 channels could be reversibly changed from zero to ∼3 times that in wild‐type mice, using tetracycline transactivator and the tetracycline responsive element. We recorded telemetric ECGs in freely moving conscious mice and analysed the heart rate variability. We also evaluated the response of the SAN to cervical vagus nerve stimulation (CVNS). The conditional overexpression of HCN4 did not induce tachycardia, but reduced heart rate variability. The HCN4 overexpression also attenuated bradycardia induced by the CVNS only during the β‐adrenergic stimulation. In contrast, the knockdown of HCN4 gave rise to sinus arrhythmia, and enhanced the parasympathetic response; complete sinus pause was induced by the CVNS. In vitro, we compared the effects of acetylcholine on the spontaneous action potentials of single pacemaker cells, and found that similar phenotypic changes were induced by genetic manipulation of HCN4 expression both in the presence and absence of β‐adrenergic stimulation. Our study suggests that HCN4 channels attenuate the vagal response of the SAN, and thereby stabilize the spontaneous firing of the SAN.

01 Sep 2017·Acta Physiologica

A mechanism for Na_V1.5 downregulation and sodium current decrease in heart failure

Communications

Author: Vergés, M. ; Pagans, S.

The pore-forming α-subunit of the cardiac voltage-gated sodium channel, NaV1.5, is responsible for the initial upstroke of the cardiac action potential. NaV1.5 cell surface expression and function are modulated by its interaction with regulatory proteins and by posttranslational modifications, such as phosphorylation, arginine methylation or ubiquitination 1. Genetic mutations in the SCN5A gene, which encodes NaV1.5, have been associated with a variety of inherited cardiac arrhythmias, including long QT syndrome type 3, Brugada syndrome, atrial fibrillation, and congenital sick sinus syndrome. In addition, abnormal NaV1.5 plasma membrane expression or sodium current (INa) density have also been observed in acquired cardiac disorders, such as heart failure (HF), although the molecular mechanisms that trigger these alterations are not well understood. This article is protected by copyright. All rights reserved.

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Sick Sinus Syndrome 1, Autosomal Recessive

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