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The Role of RyR2 Mutations in Congenital Heart Diseases: Insights Into Cardiac Electrophysiological Mechanisms.
J Cardiovasc Electrophysiol
January 2025
Department of Cardiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.
Ryanodine receptor 2 (RyR2) protein, a calcium ion release channel in the sarcoplasmic reticulum (SR) of myocardial cells, plays a crucial role in regulating cardiac systolic and diastolic functions. Mutations in RyR2 and its dysfunction are implicated in various congenital heart diseases (CHDs). Studies have shown that mutations in the RYR2 gene, which encodes the RyR2 protein, are linked to several cardiac arrhythmias, including catecholaminergic polymorphic ventricular tachycardia (CPVT), long QT syndrome (LQTS), calcium release deficiency syndrome (CRDS), and atrial fibrillation (AF).
View Article and Find Full Text PDFFlecainide Specifically Targets the Monovalent Countercurrent Through the Cardiac Ryanodine Receptor, While a Dominant Opposing Ca/Ba Current Is Present.
Int J Mol Sci
December 2024
Institute of Molecular Physiology and Genetics, Centre of Biosciences, Slovak Academy of Sciences, Dubravska cesta 9, 840 05 Bratislava, Slovakia.
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a highly arrhythmogenic syndrome triggered by stress, primarily linked to gain-of-function point mutations in the cardiac ryanodine receptor (RyR2). Flecainide, as an effective therapy for CPVT, is a known blocker of the surface-membrane Na channel, also affecting the intracellular RyR2 channel. The therapeutic relevance of the flecainide-RyR2 interaction remains controversial, as flecainide blocks only the RyR2 current flowing in the opposite direction to the physiological Ca release from the sarcoplasmic reticulum (SR).
View Article and Find Full Text PDFVimentin Intermediate Filaments Maintain Membrane Potential of Mitochondria in Growing Neurites.
Biology (Basel)
November 2024
Institute of Protein Research, Russian Academy of Sciences, 119334 Moscow, Russia.
Neural precursor cells contain two types of intermediate filaments (IFs): neurofilaments consisting of three IV type proteins and vimentin belonging to the type III IF proteins that disappear at the later stages of differentiation. The involvement of vimentin in neurogenesis was demonstrated earlier; however, the role of its temporary expression in neurons is not clear. We showed that the vimentin IFs that interacted with mitochondria maintained their membrane potential at the appropriate level, and thus, ensured their proper function.
View Article and Find Full Text PDFCatecholaminergic dysfunction drives postural and locomotor deficits in a mouse model of spinal muscular atrophy.
Cell Rep
January 2025
Center for Motor Neuron Biology and Disease, Columbia University, New York, NY 10032, USA; Department of Neurology, Columbia University, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA. Electronic address:
Article Synopsis
- Understanding posture is crucial for how mammals move, and dysregulation of certain brain chemicals, specifically dopamine and noradrenaline, can lead to motor problems in diseases like spinal muscular atrophy (SMA).
- Research using a mouse model of SMA revealed that the loss of synapses in the spinal neurons, caused by non-cell autonomous mechanisms, contributes to motor dysfunction and postural issues.
- Restoring a specific protein (survival motor neuron) in either catecholaminergic or serotonergic neurons can improve movement, but significant postural issues only improve with restoration in both neuron types or treatment with l-dopa, highlighting new potential treatment strategies.
Neuronal Regulation of Feeding and Energy Metabolism: A Focus on the Hypothalamus and Brainstem.
Neurosci Bull
December 2024
Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Key Laboratory of Immune Response and Immunotherapy, CAS Key Laboratory of Brain Function and Disease, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230026, China.
In the face of constantly changing environments, the central nervous system (CNS) rapidly and accurately calculates the body's needs, regulates feeding behavior, and maintains energy homeostasis. The arcuate nucleus of the hypothalamus (ARC) plays a key role in this process, serving as a critical brain region for detecting nutrition-related hormones and regulating appetite and energy homeostasis. Agouti-related protein (AgRP)/neuropeptide Y (NPY) neurons in the ARC are core elements that interact with other brain regions through a complex appetite-regulating network to comprehensively control energy homeostasis.
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