-related epilepsy of infancy with migrating focal seizures: report of a variant with apparent gain- and loss-of-function effects.

SCN2A encodes a voltage-gated sodium channel (Na1.2) expressed throughout the central nervous system in predominantly excitatory neurons. Pathogenic variants in are associated with epilepsy and neurodevelopmental disorders.

Novel G1481V and Q1491H SCN5A Mutations Linked to Long QT Syndrome Destabilize the Nav1.5 Inactivation State.

Background: Na1.5, which is encoded by the gene, is the predominant voltage-gated Na channel in the heart. Several mutations of this gene have been identified and reported to be involved in several cardiac rhythm disorders, including type 3 long QT interval syndrome, that can cause sudden cardiac death.

Biophysical, Molecular, and Pharmacological Characterization of Voltage-Dependent Sodium Channels From Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Background: The ability to differentiate patient-specific human induced pluripotent stem cells in cardiac myocytes (hiPSC-CM) offers novel perspectives for cardiovascular research. A number of studies, that reported mainly on current-voltage curves used hiPSC-CM to model voltage-gated Na channel (Na) dysfunction. However, the expression patterns and precise biophysical and pharmacological properties of Na channels from hiPSC-CM remain unknown.

Differential modulation of Nav1.7 and Nav1.8 channels by antidepressant drugs.

Antidepressant drugs of the SSRI family are used as a third-line treatment for neuropathic pain. In contrast MAOi antidepressants, that also increase extracellular serotonin bioavailability have little or no effects on this condition. In addition to their action of the serotonin transporter, some SSRI have been shown to inhibit voltage gated sodium channels.

Correlation of the electrophysiological profiles and sodium channel transcripts of individual rat dorsal root ganglia neurons.

Voltage gated sodium channels (Nav channels) play an important role in nociceptive transmission. They are intimately tied to the genesis and transmission of neuronal firing. Five different isoforms (Nav1.

Fluoxetine blocks Nav1.5 channels via a mechanism similar to that of class 1 antiarrhythmics.

The voltage-gated Nav1.5 channel is essential for the propagation of action potentials in the heart. Malfunctions of this channel are known to cause hereditary diseases.

Pyridoxal-5'-phosphate (MC-1), a vitamin B6 derivative, inhibits expressed P2X receptors.

P2X receptors are cation-permeable ligand-gated ion channels that open in response to the binding of ATP. These receptors are present in many excitable cells, including neurons, striated muscle cells, epithelial cells, and leukocytes. They mediate fast excitatory neurotransmission in the central and peripheral nervous systems and are thought to be involved in neuropathic pain, inflammation, and cell damage following ischemia-reperfusion injuries.

Modulation of peripheral Na(+) channels and neuronal firing by n-butyl-p-aminobenzoate.

n-butyl-p-aminobenzoate (BAB), a local anesthetic, is administered epidurally in cancer patients to treat pain that is poorly controlled by other drugs that have a number of adverse effects. The purpose of the study was to unravel the mechanisms underlying the apparent selective pain suppressant effect of BAB. We used the whole-cell patch-clamp technique to record Na(+) currents and action potentials (APs) in dissociated, nociceptive dorsal root ganglion (DRG) cells from rats, two types of peripheral sensory neuron Na(+) channels (Nav1.

A distinct de novo expression of Nav1.5 sodium channels in human atrial fibroblasts differentiated into myofibroblasts.

Fibroblasts play a major role in heart physiology. They are at the origin of the extracellular matrix renewal and production of various paracrine and autocrine factors. In pathological conditions, fibroblasts proliferate, migrate and differentiate into myofibroblasts leading to cardiac fibrosis.

Coexisting mutations/polymorphisms of the long QT syndrome genes in patients with repaired Tetralogy of Fallot are associated with the risks of life-threatening events.

Coexisting long QT gene mutations/polymorphisms in Tetralogy of Fallot (TOF) patients may aggravate the repolarization abnormality from cardiac repair. We investigated the impact of these genes on the risk of life-threatening events. Genetic variants of the three common long QT genes were identified from patients with repaired TOF.

A new C-terminal hERG mutation A915fs+47X associated with symptomatic LQT2 and auditory-trigger syncope.

Background: A novel mutation of hERG (A915fs+47X) was discovered in a 32-year-old woman with torsades de pointes, long QTc interval (515 ms), and syncope upon auditory trigger.

Objective: We explored whether the properties of this mutation could explain the pathology.

Methods: Whole-cell A915fs+47X (del) and wild-type (WT) currents were recorded in transiently transfected COS7 cells or Xenopus oocytes.

In utero onset of long QT syndrome with atrioventricular block and spontaneous or lidocaine-induced ventricular tachycardia: compound effects of hERG pore region mutation and SCN5A N-terminus variant.

Background: Mexiletine may protect patients with long QT syndrome (LQTS) type 3 from arrhythmias. However, we found an unusual in utero presentation of intermittent atrioventricular block and ventricular tachycardia (spontaneous or lidocaine-induced) in a fetus and his sibling with LQTS.

Objective: The purpose of this study was to investigate the underlying channelopathy and functional alteration.