• Atrial Fibrillation
• Electrical remodeling
• Late sodium current
• PI3K/Akt signaling
• Tachypacing

• Arrhythmias
• Heart
• Ion channels
• Transcription factors

• absolute protein quantification
• cardiac diseases
• cardiomyocytes
• ion channels
• membrane protein expression
• parallel reaction monitoring (PRM)
• protein copy numbers
• sodium voltage-gated channel alpha subunit 5 gene (SCN5A) and its corresponding protein (Nav1.5)
• targeted mass spectrometry

• SCN5A
• cardiac morphology
• development
• embryonic lethality
• non-electrogenic
• sodium current

Atrial fibrillation (AF) is known to be the most common supraventricular arrhythmia affecting up to 1% of the general population. Its prevalence exponentially increases with age and could reach up to 8% in the elderly population. The management of AF is a complex issue that is addressed by extensive ongoing basic and clinical research. AF centers around different types of disturbances, including ion channel dysfunction, Ca²⁺-handling abnormalities, and structural remodeling. Genome-wide association studies (GWAS) have uncovered over 100 genetic loci associated with AF. Most of these loci point to ion channels, distinct cardiac-enriched transcription factors, as well as to other regulatory genes. Recently, the discovery of post-transcriptional regulatory mechanisms, involving non-coding RNAs (especially microRNAs), DNA methylation, and histone modification, has allowed to decipher how a normal heart develops and which modifications are involved in reshaping the processes leading to arrhythmias. This review aims to provide a current state of the field regarding the identification and functional characterization of AF-related epigenetic regulatory networks

• atrial fibrillation
• epigenetics
• gene regulation

• Brugada syndrome
• Depolarization
• Ion channel
• Repolarization
• Risk stratification

In this case report, we characterize a novel inherited frameshift mutation c.4700_4701del (p.Phe1567Cysfs^*221) in a single copy of the SCN5A gene and its association with Brugada syndrome (BrS). The proband experienced a life-threatening ventricular arrhythmia successfully treated with DC-shock and he also suffered from supraventricular tachycardia. Ajmaline test confirmed the BrS diagnosis. No other mutation nor low frequency variants in the other 23 analyzed genes were detected. The same mutation was found in the father and sister, who were both diagnosed with BrS. We hypothesize that this mutation could be responsible for BrS and potentially linked to supraventricular tachycardias. Further studies are needed to confirm this observation and to assess the clinical relevance of this mutation, in terms of risk-stratification.

• Brugada syndrome
• SCN5A
• arrhythmia
• atrial fibrillation
• genetic testing
• mutation
• sodium channel
• sudden cardiac death

• Atrial fibrillation
• PITX2
• SNPs
• hypertension
• hyperthyroidism
• non-coding RNAs.

• Animals
• Atrial Fibrillation/genetics
• Gene Expression Regulation
• Gene Regulatory Networks
• Homeodomain Proteins/genetics
• Humans
• Polymorphism, Single Nucleotide
• Transcription Factors/genetics
• Homeobox Protein PITX2

• Arrhythmias
• Cardiology
• Cell Biology
• Potassium channels
• Sodium channels

The Brugada syndrome (BrS) is characterized by coved-type ST-segment elevation in the right precordial leads on the electrocardiogram (ECG) and increased risk of sudden cardiac death (SCD). While it is an inheritable disease, determining the true prevalence is a challenge, since patients may report no known family history of the syndrome, present with a normal spontaneous ECG pattern at the time of examination, and test negative for all known BrS-causative genes. In fact, SCD is often the first indication that a person is affected by the syndrome. Men are more likely to be symptomatic than women. Abnormal, low-voltage, fractionated electrograms have been found in the epicardium of the right ventricular outflow tract (RVOT). Ablation of this area abolishes the abnormal electrograms and helps to prevent arrhythmic recurrences. BrS patients are more likely to experience ventricular tachycardia/fibrillation (VT/VF) during fever or during an increase in vagal tone. Isoproterenol helps to reverse the ECG BrS phenotype. In this review, we discuss roles of calcium in various conditions that are relevant to BrS, such as changes in temperature, heart rate, and vagal tone, and the effects of gender and isoproterenol on calcium handling. Studies are warranted to further investigate these mechanisms in models of BrS.

• Brugada syndrome
• channelopathies
• fever
• genetic testing
• ion channel
• sudden cardiac death

• INa-L
• INa-P
• Nav1.5
• SCN5A
• gain-of-function
• loss-of-function

• CACNA1C
• Canalopatías
• Cav1.2
• Channelopathies
• I(CaL)
• I(NaL)
• Long QT syndrome
• Nav1.5
• Patch-clamp
• SCN5A
• Síndrome de QT largo

• Brugada syndrome
• Na+ Channels
• channelopathies
• sudden infant death syndrome

Atrial fibrillation (AF) is the most frequent arrhythmogenic syndrome in humans. With an estimate incidence of 1%-2% in the general population, AF raises up to almost 10%-12% in 80+ years. Thus, AF represents nowadays a highly prevalent medical problem generating a large economic burden. At the electrophysiological level, distinct mechanisms have been elucidated. Yet, despite its prevalence, the genetic and molecular culprits of this pandemic cardiac electrophysiological abnormality have remained largely obscure. Molecular genetics of AF familiar cases have demonstrated that single nucleotide mutations in distinct genes encoding for ion channels underlie the onset of AF, albeit such alterations only explain a minor subset of patients with AF. In recent years, analyses by means of genome-wide association studies have unraveled a more complex picture of the etiology of AF, pointing out to distinct cardiac-enriched transcription factors, as well as to other regulatory genes. Furthermore a new layer of regulatory mechanisms have emerged, i.e., post-transcriptional regulation mediated by non-coding RNA, which have been demonstrated to exert pivotal roles in cardiac electrophysiology. In this manuscript, we aim to provide a comprehensive review of the genetic regulatory networks that if impaired exert electrophysiological abnormalities that contribute to the onset, and subsequently, on self-perpetuation of AF.

• Atrial fibrillation
• Genetics
• MicroRNAs
• Genome-wide association studies
• PITX2