<i>SCN5A</i>
            channelopathy: arrhythmia, cardiomyopathy, epilepsy and beyond

Remme, Carol Ann

doi:10.1098/rstb.2022.0164

Cited by 17 publications

(11 citation statements)

References 179 publications

(266 reference statements)

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“…Some studies have shown that SPOCD1 [577], DRD3 [578], DOCK5 [579], SLCO6A1 [305], HTR2C [580], OTX2 [581], LMX1A [582], NR2E1 [319], GPR78 [323], RORB (RAR related orphan receptor B) [583], NTNG2 [326], PRR5-ARHGAP8 [584], CACNA2D4 [585], SLC1A2 [586], CUX2 [587], KCNH7 [588] and ACAN (aggrecan) [335] plays a certain role in bipolar disorder. The altered expression of ABCG2 [589], LAMC3 [590], CACNA1A [591], COL6A2 [592], SLC13A5 [593], GABRA2 [594], SCN5A [160], KCNQ5 [595], SLC1A2 [596], TRPC3 [597], GABRA4 [598], SLC6A11 [599], KCNQ5 [600] and SLCO5A1 [601] are associated with epilepsy. In summary, DEGs involved in GO term and REACTOME pathway were more likely related to schizophrenia and might be important targets in schizophrenia therapy.…”

Section: Discussionmentioning

confidence: 99%

Screening of the Key Genes and Signaling Pathways for Schizophrenia Using Bioinformatics and Next Generation Sequencing Data Analysis

Vastrad,

Vastrad

2023

Preprint

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Schizophrenia is thought to be the most prevalent chronic psychiatric disorder. Numerous proteins have been identified that are associated with the occurrence and development of schizophrenia. This study aimed to identify potential core genes and pathways involved in schizophrenia, through exhaustive bioinformatic and next generation sequencing (NGS) data analyses using GSE20966 NGS data of neural progenitor cells and neurons obtained from healthy controls and patients with schizophrenia. The NGS data were downloaded from the Gene Expression Omnibus database. NGS data was processed by the DESeq2 package in R software and the differentially expressed genes (DEGs) were identified. Gene Ontology (GO) enrichment analysis and REACTOME pathway enrichment analysis were carried out to identify potential biological functions and pathways of the DEGs. Protein-protein interaction (PPI) network, module, miRNA-hub gene regulatory network and TF-hub gene regulatory network analysis were performed to identify the hub genes, miRNA and TFs. Potential hub genes were analyzed using receiver operating characteristic (ROC) curves in the R package (pROC). In this investigation, an overall 955 DEGs were identified: 478 genes were remarkably up regulated and 477 genes were distinctly down regulated. These genes were enriched for GO terms and pathways mainly involved in the multicellular organismal process, GPCR ligand binding, regulation of cellular process and amine ligand-binding receptors. MYC, FN1, CDKN2A, EEF1G, CAV1, ONECUT1, SYK, MAPK13, TFAP2A and BTK were considered the potential hub genes. miRNA-hub gene regulatory network and TF-hub gene regulatory network were constructed successfully. On the whole, the findings of this investigation enhance our understanding of the potential molecular mechanisms of schizophrenia and provide potential targets for further investigation.

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Section: Discussionmentioning

confidence: 99%

Screening of the Key Genes and Signaling Pathways for Schizophrenia Using Bioinformatics and Next Generation Sequencing Data Analysis

Vastrad,

Vastrad

2023

Preprint

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“…This drives the rapid depolarizing activating phase 0 of the consequent atrial or ventricular cardiomyocyte APs. Nav1.5 shows complex functional and distribution patterns among subcellular cardiomyocyte subdomains; cardiomyocytes may further express additional Nav1.x subtypes ( Remme, 2023 ). Subsequent I Na inactivation contributes to AP recovery alterable by pathological persistent, potentially pro-arrhythmic, late, I NaL , currents ( Chadda et al, 2017 ; Yu et al, 2018 ; Liu et al, 2023 ).…”

Section: Ion Channels Underlying Normal and Abnormal Rhythmic Activitymentioning

confidence: 99%

“…At intercalated disks, Nav1.5 associates with N-cadherin, connexin-43, β IV -spectrin, and desmosomal proteins including plakophilin-2 and desmoglein-2. Gene mutations involving some of these proteins are associated with arrhythmic disorders suggesting Nav1.5 dysfunction ( Shy et al, 2013 ; Remme, 2023 ).…”

Section: Ion Channel Modulation At the Level Of The Cell Membranementioning

confidence: 99%

Cardiac arrhythmogenesis: roles of ion channels and their functional modification

Lei,

Salvage,

Jackson

et al. 2024

Front. Physiol.

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Cardiac arrhythmias cause significant morbidity and mortality and pose a major public health problem. They arise from disruptions in the normally orderly propagation of cardiac electrophysiological activation and recovery through successive cardiomyocytes in the heart. They reflect abnormalities in automaticity, initiation, conduction, or recovery in cardiomyocyte excitation. The latter properties are dependent on surface membrane electrophysiological mechanisms underlying the cardiac action potential. Their disruption results from spatial or temporal instabilities and heterogeneities in the generation and propagation of cellular excitation. These arise from abnormal function in their underlying surface membrane, ion channels, and transporters, as well as the interactions between them. The latter, in turn, form common regulatory targets for the hierarchical network of diverse signaling mechanisms reviewed here. In addition to direct molecular-level pharmacological or physiological actions on these surface membrane biomolecules, accessory, adhesion, signal transduction, and cytoskeletal anchoring proteins modify both their properties and localization. At the cellular level of excitation–contraction coupling processes, Ca2+ homeostatic and phosphorylation processes affect channel activity and membrane excitability directly or through intermediate signaling. Systems-level autonomic cellular signaling exerts both acute channel and longer-term actions on channel expression. Further upstream intermediaries from metabolic changes modulate the channels both themselves and through modifying Ca2+ homeostasis. Finally, longer-term organ-level inflammatory and structural changes, such as fibrotic and hypertrophic remodeling, similarly can influence all these physiological processes with potential pro-arrhythmic consequences. These normal physiological processes may target either individual or groups of ionic channel species and alter with particular pathological conditions. They are also potentially alterable by direct pharmacological action, or effects on longer-term targets modifying protein or cofactor structure, expression, or localization. Their participating specific biomolecules, often clarified in experimental genetically modified models, thus constitute potential therapeutic targets. The insights clarified by the physiological and pharmacological framework outlined here provide a basis for a recent modernized drug classification. Together, they offer a translational framework for current drug understanding. This would facilitate future mechanistically directed therapeutic advances, for which a number of examples are considered here. The latter are potentially useful for treating cardiac, in particular arrhythmic, disease.

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“…In the current theme issue, Salvage et al . [ 24 ], Remme [ 25 ], Terrar [ 26 ], Jung et al . [ 27 ] and He et al .…”

Section: Modern Developments In the Fieldmentioning

confidence: 99%

“…Furthermore, electrophysiological aberrations and arrhythmic tendency in the BrS and LQTS3 models were similarly accentuated or relieved by flecainide and ameliorated or accentuated by quinidine [ 53 , 60 ], findings with potential translational significance [ 61 , 62 ]. Remme [ 25 ] reviews complex Nav1.5 functional and distribution patterns involving particular subcellular cardiomyocyte subdomains, as well as non-canonical non-electrogenic Nav1.5 actions with structural, potentially cardiomyopathic and pro-arrhythmic, effects. Finally, Nav1.5 does occur in other cell types, including various extracardiac tissues.…”

Section: Ion Channels Contributing To Cardiomyocyte Surface Membrane ...mentioning

confidence: 99%

Cardiomyocyte electrophysiology and its modulation: current views and future prospects

Huang

Lei

2023

Phil. Trans. R. Soc. B

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Normal and abnormal cardiac rhythms are of key physiological and clinical interest. This introductory article begins from Sylvio Weidmann's key historic 1950s microelectrode measurements of cardiac electrophysiological activity and Singh & Vaughan Williams's classification of cardiotropic targets. It then proceeds to introduce the insights into cardiomyocyte function and its regulation that subsequently emerged and their therapeutic implications. We recapitulate the resulting view that surface membrane electrophysiological events underlying cardiac excitation and its initiation, conduction and recovery constitute the final common path for the cellular mechanisms that impinge upon this normal or abnormal cardiac electrophysiological activity. We then consider progress in the more recently characterized successive regulatory hierarchies involving Ca 2+ homeostasis, excitation–contraction coupling and autonomic G-protein signalling and their often reciprocal interactions with the surface membrane events, and their circadian rhythms. Then follow accounts of longer-term upstream modulation processes involving altered channel expression, cardiomyocyte energetics and hypertrophic and fibrotic cardiac remodelling. Consideration of these developments introduces each of the articles in this Phil. Trans. B theme issue. The findings contained in these articles translate naturally into recent classifications of cardiac electrophysiological targets and drug actions, thereby encouraging future iterations of experimental cardiac electrophysiological discovery, and testing directed towards clinical management. This article is part of the theme issue ‘The heartbeat: its molecular basis and physiological mechanisms’.

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SCN5A channelopathy: arrhythmia, cardiomyopathy, epilepsy and beyond

Cited by 17 publications

References 179 publications

Screening of the Key Genes and Signaling Pathways for Schizophrenia Using Bioinformatics and Next Generation Sequencing Data Analysis

Screening of the Key Genes and Signaling Pathways for Schizophrenia Using Bioinformatics and Next Generation Sequencing Data Analysis

Cardiac arrhythmogenesis: roles of ion channels and their functional modification

Cardiomyocyte electrophysiology and its modulation: current views and future prospects

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