Cardiac channel mutations. Medical search. Frequent questions

In conclusion, decreased or increased protein expression of several TRPM4 variants linked to cardiac conduction disorders or ventricular arrhythmias were found to be caused by altered TRPM4 half-life compared to the WT form. (frontiersin.org)
These patients exhibit prolonged QT interval and lethal cardiac arrhythmias. (sanevax.org)
The principal cause of sudden death is the occurrence of malignant cardiac arrhythmias, which result in the loss of contraction of the heart with subsequent lack of blood supply to vital organs like the brain. (escardio.org)
In all of them, the final result is the occurrence of malignant ventricular arrhythmias (polymorphic ventricular tachycardia or ventricular fibrillation) responsible for sudden cardiac death. (escardio.org)
The authors' findings, published online this week by the peer-reviewed journal Nature Medicine , suggest that mutations of either of two gene products -- proteins called KCNE2 and KCNQ1 -- already known to be involved in human cardiac arrhythmias, could also cause thyroid dysfunction. (sciencedaily.com)
It has long been known that the thyroid influences cardiac function and cardiac arrhythmias," says study senior author Dr. Geoffrey W. Abbott, associate professor of pharmacology in medicine at Weill Cornell Medical College, "but our findings demonstrate a novel genetic link between inherited cardiac arrhythmia and thyroid dysfunction. (sciencedaily.com)
Additionally, it is the authors' suggestion that assessment of the thyroid status of patients with KCNE2- and KCNQ1-linked cardiac arrhythmias could in some cases reveal a potential endocrine component to their cardiac arrhythmias that may not have been previously determined. (sciencedaily.com)
Inherited mutations in KCNQ1 and KCNE2 cause ventricular and atrial cardiac arrhythmias, previously presumed to be due entirely to the role of these proteins in cardiac muscle. (sciencedaily.com)
When the thyroid does not produce enough TH, a person may experience symptoms such as fatigue and a lowered heart rate, but there is also a more complex interplay between thyroid function, cardiac structure and cardiac arrhythmias. (sciencedaily.com)
Cardiac arrhythmias affect up to three million people in the United States. (sciencedaily.com)
Ventricular arrhythmias account for the large majority of the 300,000 cases of sudden cardiac death annually in the United States. (sciencedaily.com)
They also explored its potential as a therapeutic drug for use in preventing cardiac arrhythmias. (the-scientist.com)
CONCLUSIONS: This study demonstrates which mutations can prolong APD sufficiently to generate early afterdepolarizations (EADs), which may trigger life-threatening arrhythmias. (cellml.org)
Torsades de pointes should be differentiated from other conditions or disorders that may present in a similar way, such as other arrhythmias , drug toxicity, syncope and other cardiac conditions. (wikidoc.org)
Mutations in SCN5A, encoding the cardiac sodium (Na) channel, are linked to a form of the congenital long-QT syndrome (LQT3) that provokes lethal ventricular arrhythmias. (johnshopkins.edu)
The ventricular arrhythmias may cause palpitations, and/or cardiac arrest. (msdmanuals.com)

If untreated, the arrhythmia associated with short QT syndrome can lead to a variety of signs and symptoms, from dizziness and fainting (syncope) to cardiac arrest and sudden death. (medlineplus.gov)
Long QT syndrome (LQTS) is a congenital disorder characterized by a prolongation of the QT interval on electrocardiograms (ECGs) and a propensity to ventricular tachyarrhythmias, which may lead to syncope, cardiac arrest, or sudden death. (medscape.com)
LQTS is usually diagnosed after a person has a cardiac event (eg, syncope, cardiac arrest). (medscape.com)
However, such an examination is necessary to exclude other potential cardiac causes of syncope or cardiac arrest in an otherwise healthy patient (eg, heart murmurs from hypertrophic cardiomyopathy or from a valvular or septal defect). (medscape.com)
BS presents with syncope and/or cardiac arrest due to ventricular fibrillation in normal structural heart. (alliedacademies.org)
range, 1 to 10) events of syncope or unexplained seizure that remained undiagnosed as a cardiac disorder before SCA. (jabfm.org)
Patients who are being evaluated for torsades de pointes should be asked about a history of syncope, and family history of long QT syndrome , sudden cardiac death , or sudden infant death syndrome . (wikidoc.org)
Patients present clinically with a spectrum of signs and symptoms including irregular palpitations due to episodes of paroxysmal atrialfibrillation, dizziness and fainting (syncope) and/or sudden cardiac death due to polymorphic ventricular tachycardia and ventricular fibrillation. (viamedica.pl)

Finally, it seems appropriate to consider the "sodium channel syndrome" (mutations in the gene of the α subunit of the sodium channel, SCN5A gene) as a single clinical entity that may manifest in a wide range of phenotypes, to thus have a better insight on these cardiac syndromes and potential outcomes for their clinical treatment. (bvsalud.org)
Because IVF causes cardiac rhythm disturbance, we investigated whether malfunction of ion channels could cause the disorder by studying mutations in the cardiac sodium channel gene SCN5A. (nih.gov)
We have now identified a missense mutation, a splice-donor mutation, and a frameshift mutation in the coding region of SCN5A in three IVF families. (nih.gov)
Mutations in the gene SCN5a is the most common genetic cause of Brugada Syndrome (BS), a rare inherited cardiac channelopathy, characterized by ST-segment elevation in the right pericardial leadsV1-V3 and right bundle-branch block. (alliedacademies.org)
SCN5a encodes an α-subunit of the cardiac voltage-gated sodium channel (Nav1.5) at 3p21 with 28 exons encoding 2016 amino acids. (alliedacademies.org)
More than 400 mutations are describedand up of 150 mutations are located in domains III and IV of SCN5a. (alliedacademies.org)
The aim was the optimisation of a genetic screening method for causative mutation in domain III and IV of SCN5a using High Resolution Melting (HRM). (alliedacademies.org)
This study will define hotspot mutations in domain III and IV of SCN5a in Tunisian Brugada patients and families, to improve the genetics counseling and therapeutic management. (alliedacademies.org)
Human genetic studies have identified mutations in the sodium channel SCN5A gene causing tachyarrhythmia disorders, as well as progressive cardiac conduction system diseases, or overlapping syndromes. (medscape.com)

Behavioral and pharmacological studies of these mutants may provide insight into the genetic and mechanistic basis of K + channel dysfunction in vivo . (jneurosci.org)
Chris' primary research focus is on using experimental and clinical data to predict how heart cells, the engine of every heartbeat, respond to genetic mutations and to drugs. (swansea.ac.uk)
These are basically familial diseases, based on the presence of genetic defects in some of the electrical channels of the heart. (escardio.org)
Molecular genetic technology is currently used in forensic investigations to detect mutations in cardiac ion channels causing long QT syndrome, which can explain a previously sudden unexplained death in an adult (SUDS) or infant (SIDS). (confex.com)
The team achieved this feat by making three CRISPR edits in a single gene: modifications identical to the genetic mutations that allow monarch butterflies to dine on milkweed and sequester its poison. (labmanager.com)
Flies with the triple genetic mutation proved to be 1,000 times less sensitive to milkweed toxin than the wild fruit fly, Drosophila melanogaster. (labmanager.com)
Each of us inherits hundreds of genetic mutations from our parents, as they did from their forebears. (dorak.info)
Drugs can then be tested on these pairs to determine with certainty that the results are due to the mutation and not background genetic anomalies between cell lines. (drugdiscoverynews.com)
These problems could be solved if we had a method to grow human heart cells from people with genetic LQTS mutations, so that we know the exact test conditions that would reflect the human disease. (ca.gov)
These studies will provide the foundation for an expanded panel of iPS cell lines from people with other genetic mutations and from people who have no genetically defined risk factor but still have potentially fatal drug-induced LQTS. (ca.gov)
Among evidence considered by the 2019 inquiry were "molecular autopsies" on the two female Folbigg children - one of whom died at 10 months and the other at 18 months - which found they had genetic mutations that predispose to sudden cardiac death. (cosmosmagazine.com)
While the two children were found to have genetic mutations there was no "functional validation" or hard data at the time to show the variants were likely to have caused a fatal heart event. (cosmosmagazine.com)
These 3 potassium channel variants are the "genetic mirror image" of long QT syndrome type 2, type 1 and Andersen-Tawil syndrome respectively because they exert opposite gain-of-function effects on the potassium channels in contrast to the loss-of-function of the potassium channels in the long QT syndromes. (viamedica.pl)
This review focuses the landmarks of this newest arrhythmogenic cardiac channelopathy on the main clinical, genetic, and proposed ECG mechanisms. (viamedica.pl)
Early repolarization syndrome is a genetic disorder of cardiomyocyte ion channel function (channelopathy). (msdmanuals.com)

Our research focuses on Long QT syndrome, a cardiac disorder that can lead to fatal arrythmias. (tu.edu)
Causes of Long QT syndrome include metabolic dysfunction, mutations in cardiac ion channels, and medications that disrupt cardiac ion channel function. (tu.edu)
ABSTRACT: BACKGROUND: A variety of mutations in HERG, the major subunit of the rapidly activating component of the cardiac delayed rectifier I(Kr), have been found to underlie the congenital Long-QT syndrome, LQT2. (cellml.org)
Cellular consequences of HERG mutations in the long QT syndrome: precursors to sudden cardiac death, Colleen E. Clancy and Yoram Rudy, 2001, Cardiovascular Research , 50, 301-313. (cellml.org)
Calmodulin variant E140G associated with long QT syndrome impairs CaMKIIδ autophosphorylation and L-type calcium channel inactivation. (nih.gov)
Beta-blocker Efficacy in Long QT Syndrome Patients with Mutations in the Pore and Nonpore Regions of the hERG Potassium-channel Gene. (heartandcoeur.com)
Long QT syndrome is a risk factor for developing torsades de pointes, and can either be inherited as congenital mutations of ion channels carrying the cardiac impulse/action potential, or acquired as a result of drugs that block these cardiac ion currents. (wikidoc.org)
Nearly 500,000 people in the US die of sudden cardiac death each year, and long QT syndrome (LQTS) is a major form of sudden cardiac death. (ca.gov)
Mutation location and IKs regulation in the arrhythmic risk of long QT syndrome type 1: the importance of the KCNQ1 S6 region. (cdc.gov)

A missense mutation (T75R) of Kir2.1, located in the highly conserved cytoplasmic N-terminal domain, was identified in three affected members of this family. (nih.gov)
We show that sodium channels with the missense mutation recover from inactivation more rapidly than normal and that the frameshift mutation causes the sodium channel to be non-functional. (nih.gov)
Two pseudogenes have been identified on chromosome 7 and X. Multiple transcript variants encoding different isoforms have been found for this gene.A missense mutation in the CALM1 gene has been associated with ventricular tachycardia. (nih.gov)
Kinact: a computational approach for predicting activating missense mutations in protein kinases. (lu.se)
Establishing the precise evolutionary history of a gene improves prediction of disease-causing missense mutations. (lu.se)

Sodium channel subunit beta-3 is a protein that in humans is encoded by the SCN3B gene. (wikipedia.org)
Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit and one or more regulatory beta subunits. (wikipedia.org)
This gene encodes one member of the sodium channel beta subunit gene family, and influences the inactivation kinetics of the sodium channel. (wikipedia.org)
Sodium channel ß1 subunit mutations associated with Brugada syndrome and cardiac conduction disease in humans. (yale.edu)
Mutations in four genes have been identified in familial hemiplegic migraine (FHM), from which CACNA1A (FHM type 1) and SCN1A (FHM type 3) code for neuronal voltage-gated calcium or sodium channels, respectively, while ATP1A2 (FHM type 2) encodes the α 2 isoform of the Na + ,K + -ATPase's catalytic subunit, thus classifying FHM primarily as an ion channel/ion transporter pathology. (frontiersin.org)
According to the affected ion channel subunit, LQTS is classified into six subtypes with partially different clinical courses and triggers of torsade de pointes. (asahq.org)

Early repolarization syndrome appears to be inheritable, but disease-specific gene mutations are rarely identified, suggesting that the disorder is often polygenic. (msdmanuals.com)
Although causative gene mutations have been well characterized for LGMD, no specific treatment is available for any of the LGMD syndromes yet. (medscape.com)
Overlap exists with Congenital Muscular Dystrophy (CMD) as several gene mutations can cause both a LGMD and CMD phenotype. (medscape.com)

The transient receptor potential melastatin 4 (TRPM4) protein is an intracellular Ca 2+ -activated non-selective cation channel, which is impermeable to Ca 2+ . (frontiersin.org)
They believe that, normally, the KCNQ1-KCNE2 potassium channel helps another protein (the sodium/iodide symporter) to transport iodide into the thyroid. (sciencedaily.com)
Three years after the initial discovery, they found that another protein structurally related to glutathione transferases, a chloride intracellular ion channel, CLIC-2, could also dampen the activity of the ryanodine receptor in the heart. (the-scientist.com)
FHM type 4 is attributed to mutations in the PRRT2 gene, which encodes a proline-rich transmembrane protein of as yet unknown function. (frontiersin.org)
Then, a survey is given about ATP1A2 mutations implicated in migraine cases as documented in the literature with focus on mutations that were described to completely destroy enzyme function, or lead to misfolded or mistargeted protein in particular model cell lines. (frontiersin.org)
This gene encodes a protein that has been shown to function as a guanine nucleotide release factor in mouse and to regulate the expression and function of the Nav1.5 cardiac sodium channel in human. (nih.gov)
Mechanistic insights into the interaction of the MOG1 protein with the cardiac sodium channel Na(v)1.5 clarify the molecular basis of Brugada syndrome. (nih.gov)
Kin-Driver: a database of driver mutations in protein kinases. (lu.se)
wKinMut: an integrated tool for the analysis and interpretation of mutations in human protein kinases. (lu.se)
We verified this finding by sequencing full viral genomes and confirmed a virus variant that has sporadic mutations through the full genome sequence in the spike protein (G75V and C1247F). (cdc.gov)

Pathological variants in TRPM4 gene have been linked to several cardiac phenotypes such as complete heart block (CHB), ventricular tachycardia, and Brugada syndrome (BrS). (frontiersin.org)
In contrast, the loss-of-function mutations of CaV1.2 channel in patients with Brugada syndrome produce short QT interval that could result in sudden cardiac death. (sanevax.org)
To date, the only treatment that has proven effective in treating ventricular tachycardia and fibrillation and preventing sudden death in patients with Brugada syndrome is implantation of an automatic implantable cardiac defibrillator (ICD). (medscape.com)

KCNQ1 and KCNE2 were each recognized more than a decade ago as forming potassium channels in cardiac muscle that help end each heartbeat in a timely fashion. (sciencedaily.com)
TWIK-related acid-sensitive potassium channel 1 (TASK-1 encoded by KCNK3) belongs to the family of two-pore domain potassium channels. (ersjournals.com)
Only few studies have focused on QT heterogeneity or ion channel physiology, and it seems that all volatile anesthetics-including isoflurane-interact directly with cardiac delayed rectifier potassium channels. (asahq.org)
A few families have been identified with specific genotypes: 3 with mutations in potassium channels called SQT1 (I ks ), SQT2 (I kr ) and SQT3 (I k1 ). (viamedica.pl)
Luo-Rudy dynamic model in 1994 not only includes the sodium and potassium channels in Luo-Rudy passive model but also introduces sodium-potassium pump, calcium pump, L-type calcium channel, non-specific calcium-activated channel, sodium-calcium exchanger on the membrane as well as calcium-induced calcium release channel and calcium pump on the membrane of sarcoplasmic reticulum with calcium buffers in the myoplasm. (scholarpedia.org)

TS patients also suffer from multi-organ dysfunction that includes neurological disorder such as autism and mental retardation reflecting the wide tissue distribution of CaV1.2 channel. (sanevax.org)
These studies suggest that the mutational locus may be important in the mechanism of Ca 2+ channel dysfunction. (silverchair.com)

Andersen-Tawil syndrome (ATS) is a rare inherited disorder, characterised by periodic paralysis, cardiac dysarrhythmias, and dysmorphic features, and is caused by mutations in the gene KCNJ2, which encodes the inward rectifier potassium channel, Kir2.1. (nih.gov)

These autosomal dominant mutations disrupt Na channel function, inhibiting channel inactivation, thereby causing a sustained ionic current that delays cardiac repolarization. (johnshopkins.edu)
Rather, the mutant channels have a propensity to inactivate without ever opening ('closed-state inactivation'), and lidocaine augments this gating behavior. (johnshopkins.edu)
Outcomes Intracellular Ca2+ stabilizes NaV1.5 delKPQ inactivation We analyzed the consequences of intracellular Ca2+ for the inactivation of both wildtype (WT) and mutant NaV1.5 channels. (biosemiotics2013.org)
As noticed for most LQTS-associated NaV1.5 mutations delKPQ caused an inactivation defect manifested as increased late sodium current (INaL). (biosemiotics2013.org)

Within a few months, Dulhunty and her colleagues published their first paper on the role of the omega class glutathione S-transferase, GSTO1-1, in inhibiting the ryanodine receptor in cardiac muscle and in increasing the activity of the skeletal muscle ryanodine receptor. (the-scientist.com)
Role of ryanodine receptor mutations in cardiac pathology: more questions than answers? (silverchair.com)

More than 300 mutations in six genes encoding cardiac ion channel subunits and ankyrin B have been identified in patients with LQTS. (asahq.org)
There are a myriad of mutations identified in genes encoding cardiac transcription factors, ion channels, gap junctions, energy metabolism regulators, lamins and other structural proteins. (medscape.com)

8, , 9, , 10, , 11 We therefore propose to avoid this class of anesthetics and would prefer propofol as the anesthetic of choice until more information is available from pharmacologic studies that focus on ion channel physiology and transmural heterogeneity of repolarization. (asahq.org)
Diagnosis should be considered in patients who have had polymorphic ventricular tachycardia, ventricular fibrillation, or sudden cardiac arrest (or a family history of those events in the absence of structural heart disease) and who also have ECG changes showing an inferior and/or lateral early repolarization pattern. (msdmanuals.com)

Here, we will discuss how alternative splicing modulates CaV1.2 channelopathy and the role of CaV1.2 channel in both excitable and non-excitable tissues. (sanevax.org)
Congenital or familial short QT syndrome is a genetically heterogeneous cardiac channelopathy without structural heart disease that has a dominant autosomal or sporadic pattern of transmission affecting the electric system of the heart. (viamedica.pl)

Recently, single-residue mutations in the cardiac RyR (RyR2) have been identified in families that exhibit CPVT (catecholaminergic polymorphic ventricular tachycardia), a condition in which physical or emotional stress can trigger severe tachyarrhythmias that can lead to sudden cardiac death. (silverchair.com)

Mutations in the gene are associated with abnormal cardiac electrophysiology. (wikipedia.org)
Dulhunty had set up electrophysiology experiments on a receptor from mammalian cardiac muscle fiber to measure its activity, and her initial measurements on the receptor's activity were going nicely. (the-scientist.com)
Clarifying how defects in HERG can lead to impaired cellular electrophysiology can improve our understanding of the link between channel structure and cellular function. (cellml.org)

Finally, another variant with mixed phenotype affecting the sodium channel was reported. (viamedica.pl)
Notably, LGMD subtypes are phenotypically highly variable, limb-girdle weakness may not be the predominant presentation, and mutation in genes assigned to LGMD subtypes may cause allelic conditions with a different phenotype. (medscape.com)
Some mutations can cause both a myofibrillar myopathy and a muscular dystrophy phenotype. (medscape.com)
These diseases are discussed here in part because mutations in 2 genes can present with either an LGMD or a myofibrillar myopathy phenotype. (medscape.com)

The research in our laboratory focuses on one cardiac potassium channel (called HERG). (tu.edu)
Studies involving electrical recordings of cells containing the cardiac potassium channel HERG. (tu.edu)
The goal of these studies is to determine if imbalances in extracellular electrolytes such as potassium, calcium, and magnesium can impact the cardiac potassium channel HERG, and thus could be risk factors for Long QT. (tu.edu)
RESULTS: Using this virtual transgenic cell model, we describe the effects of HERG mutations on the cardiac ventricular action potential (AP) and provide insight into the mechanism by which each defect results in a net loss of repolarizing current and prolongation of APD. (cellml.org)

To test this hypothesis we compared the effect of high and low [Ca2+]i on INaL in cells expressing either WT-NaV1.5 or delKPQ channels. (biosemiotics2013.org)

Suppression of egl-2(gf) phenotypes by imipramine likely results from the block of EGL-2( gf ) channels. (jneurosci.org)
LQT2 may give rise to severe arrhythmogenic phenotypes leading to sudden cardiac death. (cellml.org)
Three new variants with overlapping phenotypes affecting the slow inward calcium channels havealso been described. (viamedica.pl)
For example, mutations in TTN gene may present with a wide range of phenotypes ranging from congenital myopathy to late-onset distal myopathy. (medscape.com)

Ryanodine is an ion channel, embedded in an internal membrane within the muscle cell, that surrounds a pocket of calcium ions. (the-scientist.com)
The channel regulates the changes in calcium ion concentration that control the muscle contractile apparatus and, in turn, muscle movement. (the-scientist.com)
Calcium-induced activation of calmodulin regulates and modulates the function of cardiac ion channels. (nih.gov)
Cardiac enzymes and levels of potassium , magnesium and calcium should be obtained. (wikidoc.org)
Those finely tuned shifts in charge are triggered by ion channels that open and close to admit and release sodium, potassium and all-important calcium ions in quick succession. (cosmosmagazine.com)
Calmodulin closes the ion channels through which calcium flits in and out of the heart muscle cells. (cosmosmagazine.com)
But if you have the CALM2 G114R variant, calmodulin gets bad at closing the channel - it stays open and calcium can come and go as it pleases. (cosmosmagazine.com)
At the early 1980s, the ion channels in cardiac cells were not as clear as neurons , especially the channels concerned with calcium ions including those in the sarcoplasmic reticulum. (scholarpedia.org)
Dr. Luo decided to update the sodium and potassium ion channels since calcium ion channels were under debate in 1980s. (scholarpedia.org)
In 1991, the most arguing issue to formulate a live cardiac cell model was the ambiguity of the calcium ion channels. (scholarpedia.org)
Several famous labs announced the calcium ion channels but they were quite scattering with apparent differences, including species. (scholarpedia.org)
Dr. Luo made a decision to skip the debate issue but, instead, put them all into the cell model to see how action potentials look like by using those published experimental data for calcium ion channels, especially sodium-calcium exchangers. (scholarpedia.org)
It left the choice for scientists to pick up the calcium ion channels they wanted even Dr. Luo had suggestions in the Luo-Rudy dynamic model published in 1994. (scholarpedia.org)
Sodium channel is closed very quickly (in 2 msec), then the opening of potassium and calcium channels fight against to maintain the intracellular potential at the positive level called the potential plateau for 200-300 msec. (scholarpedia.org)
In contrast to nonpacemaker cells, SA and AV nodal cells predominantly use calcium channels for the initial upstroke in phase 0 (Fig. 1) and lack sodium ion channels for the rapid initial upstroke in phase 1 of their action potentials. (medscape.com)

Calmodulin Interactions with Voltage-Gated Sodium Channels. (nih.gov)

The prevalence of warning signs or symptoms in children and young adults who later suffer SCA is highly variable and poses a challenge to identifying through screening persons at elevated risk of sudden cardiac death (SCD). (jabfm.org)

A history of cardiac events is the most typical clinical presentation in patients with LQTS. (medscape.com)
We will characterize iPS cells with well-defined mutations that have clinically proven responses to drugs that cause LQTS. (ca.gov)
To meet these goals, we made a series of iPS cells that harbor different LQTS mutations. (ca.gov)

Despite recent findings regarding the functional implications of TRPM4 in cardiac diseases, the molecular and cellular mechanisms leading to altered conduction are poorly understood. (frontiersin.org)
From a physiological and pathophysiological point of view, the conformational states of the sodium channel during heart function constitute a significant aspect for the diagnosis and treatment of heart diseases. (bvsalud.org)
The patients affected with sudden death are basically those with cardiac diseases, like coronary artery disease, dilated or hypertrophic myocardiopathy, arrhythmogenic right ventricular dysplasia and others (1). (escardio.org)
1 , 2 The causes of pediatric and young adult SCA involve a heterogeneous group of cardiac diseases including structural cardiovascular abnormalities, such as cardiomyopathies, and primary cardiac electrical diseases, such as ion channel disorders. (jabfm.org)
Abnormalities in cardiac conduction can occur due to a variety of factors, including developmental and congenital defects, acquired injury or ischemia of portions of the conduction system, or less commonly due to inherited diseases that alter cardiac conduction system function. (medscape.com)

Histiocytoid cardiomyopathy and compound CACNA2D1 and RANGRF mutation in a baby. (nih.gov)

The objective of this study was to determine the prevalence of warning symptoms and family history in a cohort of children and young adults who suffered sudden cardiac arrest (SCA). (jabfm.org)
Sudden cardiac arrest (SCA) is the leading cause of nontraumatic sudden death in children and young adults and usually is the result of an undiagnosed cardiovascular disorder. (jabfm.org)

Recent studies show that modulation of TASK-1 channels, either directly or indirectly by targeting their regulatory mechanisms, has the potential to control pulmonary arterial tone in humans. (ersjournals.com)
Leiden University 's Christine Mummery, meanwhile, talked about the challenges of studying cardiac ion channels not only in mouse models, which offer a very different physiology from humans, but even between cultures of diseased and control human cardiomyocytes. (drugdiscoverynews.com)
Unfortunately, cardiac physiology in animal models (rabbits and dogs) differs from that in humans, and hamster cells lack many key features of human heart cells. (ca.gov)

Strikingly diverse functional abnormalities have been identified for disease-linked ATP1A2 mutations which frequently lead to changes in the enzyme's voltage-dependent properties, kinetics, or apparent cation affinities, but some mutations are truly deleterious for enzyme function and thus cause full haploinsufficiency. (frontiersin.org)
Understanding of the molecular and ionic mechanisms underlying cardiac conduction is essential for the appreciation of the pathogenesis of conduction abnormalities in structurally normal and altered hearts. (medscape.com)

Similar inhibition is observed with the mouse homolog MEAG, suggesting that inhibition of EAG-like channels may mediate some clinical side effects of this class of antidepressants. (jneurosci.org)
Mutations in K + channel sequences can lead to a variety of clinical disorders exemplifying their physiological importance [ 3 ]. (ersjournals.com)

The gain-of-function mutations were found at two mutually exclusive exons in patients with Timothy syndrome (TS). (sanevax.org)
Unexpectedly, TS patients may develop recurrent infections and bronchitis that suggests a role of CaV1.2 channel in the immune system. (sanevax.org)
Sodium channel- blocking antiarrhythmics, such as lidocaine, potently inhibit this pathologic Na current (I(Na)) and are being evaluated in patients with LQT3. (johnshopkins.edu)

Functional states of the sodium channel (closed, open, and inactivated) and their structure help to understand the cardiac regulation processes. (bvsalud.org)
There are areas in the cardiac muscle with anatomical and functional differentiation that present automatism, thus subjecting the rest of the fibers to their own rhythm. (bvsalud.org)
Heart relaxation also stands out as an active process, dependent on the energetic output and on specific ion and enzymatic actions, with the role of sodium channel being outstanding in the functional process. (bvsalud.org)
This review summarises our current state of knowledge of the functional role of TASK-1 channels in the pulmonary circulation in health and disease, with special emphasis on current advancements in the field. (ersjournals.com)
Here we report that a recently identified LQT3 mutation (R1623Q) imparts unusual lidocaine sensitivity to the Na channel that is attributable to its altered functional behavior. (johnshopkins.edu)

We show that the Caenorhabditis elegans egl-2 gene encodes an eag K + channel and that a gain-of-function mutation in egl-2 blocks excitation in neurons and muscles by causing the channel to open at inappropriately negative voltages. (jneurosci.org)

These findings explain the unusual drug sensitivity of R1623Q and provide a general and unanticipated mechanism for understanding how Na channel-blocking agents may suppress the pathologic, sustained Na current induced by LQT3 mutations. (johnshopkins.edu)
Methods KDM3A antibody and Outcomes We tested this notion by examining the consequences of differing intracellular Ca2+ concentrations on the amount of INaL in cells expressing an average LQT3 mutation delKPQ and another mutation R225P. (biosemiotics2013.org)

The heart achieves the coordinated contraction of the atrial and ventricular chambers due to the precise timing of the cardiac conduction system (CCS), a specialized complex and heterogeneous network of cells that initiate and allow propagation of action potentials through the heart. (medscape.com)

All K + channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). (embl.de)
K + channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. (embl.de)
In addition, there are K + channel alpha-subunits that possess two P-domains. (embl.de)

In cardiac muscle, these ion channels play critical roles in maintaining the heart's normal rhythm. (medlineplus.gov)
The only way to avoid the fatal outcome is to restore the normal cardiac rhythm by means of an electrical cardioversion or in some cases by using a pacemaker. (escardio.org)

The cardiac conduction system can be anatomically, developmentally, and molecularly distinguished from the working myocardium. (medscape.com)

Gene Therapy for Cardiac Tachyarrhythmias. (heartandcoeur.com)

The normal cardiac impulse of the vertebrate heart originates in the pacemaker cells of the sinoatrial node, located in the right atrium. (medscape.com)

The RyR2 mutations in CPVT are clustered in the N- and C-terminal domains, as well as in a central domain. (silverchair.com)
We have prepared cardiac RyR2 plasmids with various CPVT mutations to enable expression and analysis of Ca 2+ release mediated by the wild-type and mutated RyR2. (silverchair.com)

The mechanism underlying this effect is unknown, although high-affinity 'block' of the open Na channel pore has been proposed. (johnshopkins.edu)
Studies of lidocaine on individual R1623Q single-channel openings indicate that the open-time distribution is not changed, indicating the drug does not block the open pore as proposed previously. (johnshopkins.edu)

The mechanisms of cellular excitability and propagation of electrical signals in the cardiac muscle are very important functionally and pathologically. (bvsalud.org)
This 'Molecular Perspectives' will highlight several diverse mechanisms of isolated conduction system disease as well as conduction system degeneration associated with other cardiac and non-cardiac disorders. (medscape.com)

Transient receptor potential melastatin member 4 (TRPM4), a non-selective cation channel, mediates cell membrane depolarization in immune response, insulin secretion, neurological disorders, and cancer. (frontiersin.org)
The ion channels I f and I Ca,T are responsible for this slow depolarization in phase 4 (Fig. 1). (medscape.com)

Mutations in the KCNH2 , KCNJ2 , and KCNQ1 genes can cause short QT syndrome. (medlineplus.gov)
Some affected individuals have a family history of short QT syndrome or related heart problems and sudden cardiac death. (medlineplus.gov)
Entre le 19 avril et le 23 juin 2015, 52 cas confirmés en laboratoire de syndrome respiratoire du Moyen-Orient (MERS) causé par le coronavirus ont été notifiés dans la région d'Al-Ahssa, partie orientale de l'Arabie saoudite. (who.int)

Dominant negative mutations (where mutation on one copy renders the other copy inactive) are involved in osteogenesis imperfecta type I and autosomal dominant nephrogenic diabetes insidipus . (dorak.info)
This list continues to expand, and, as of this writing, specific mutations listed on OMIM are known for 7 autosomal dominant LGMDs and 23 autosomal recessive LGMDs. (medscape.com)

Because of SARS-CoV-2 outbreaks in mink farms and their appearance in the surrounding communities, the European Centre for Disease Prevention and Control and the World Health Organization have emphasized the need for surveying the host‒animal interface by collaboration among virologists and epidemiologists to track and characterize viral mutations ( 11 ). (cdc.gov)

Three of them, p.A101T, p.S1044C and a double variant p.A101T/P1204L, led to a decreased expression and function of the channel. (frontiersin.org)
However, the physiological role for this channel in cardiac function remains unclear. (frontiersin.org)
Here we report that the behavioral defects in the C. elegans egl-2 mutant are caused by a gain-of-function ( gf ) mutation in an eag-like K + channel. (jneurosci.org)
This, in turn, could indicate treatment of the thyroid condition, with potentially beneficial effects on cardiac function. (sciencedaily.com)
While we have identified KCNQ1 and KCNE2 in both mouse and human thyroid, much additional work is required before we can fully understand how inherited mutations in the genes coding these proteins affect human thyroid function, how this in turn influences the health of human heart and other tissues, and how useful our discoveries will be in developing therapies to treat thyroid and thyroid-related human disease," explains Dr. Abbott. (sciencedaily.com)
She did not expect anything to happen, but the addition of the enzyme blocked the cardiac ryanodine receptor's function. (the-scientist.com)

Mutations found on different mutually exclusive exons determine the severity of the disease. (sanevax.org)
Calmodulin Mutations in Human Disease. (nih.gov)
Management recommendations in this book are based on the established European Guidelines, which encompass the best techniques to use with each cardiac disease you are faced with. (heartandcoeur.com)
point stop mutations), hemophilia ( A , B ), phenylketonuria -PKU (point mutation), Duchenne muscular dystrophy (DMD) , adenosine deaminase (ADA) deficiency causing severe combined immune deficiency (SCID), Tay-Sachs disease (hexosaminidase A deficiency). (dorak.info)

These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. (embl.de)

Kuo, 1998 ), but the molecular identities of these channels are unknown. (jneurosci.org)

Mutations in the KCNH2 , KCNJ2 , or KCNQ1 gene increase the activity of the channels, which enhances the flow of potassium ions across the membrane of cardiac muscle cells. (medlineplus.gov)

Coronary sinus, normally located between the LEFT ATRIUM and LEFT VENTRICLE on the posterior surface of the heart, can serve as an anatomical reference for cardiac procedures. (bvsalud.org)

Anatomy18

Organisms14

Diseases25

Chemicals and Drugs104

Analytical, Diagnostic and Therapeutic Techniques and Equipment32

Phenomena and Processes64

Disciplines and Occupations3

Technology, Industry, Agriculture1

Information Science4

Health Care2

Arrhythmias16

Syncope8

SCN5A9

Genetic15

Long QT syndr9

Missense5

Subunit6

Gene mutations3

Protein10

Brugada3

Potassium Channels5

Dysfunction2

Inherited disorder1

Inactivation4

Ryanodine receptor2

Genes encodin2

Repolarization2

Channelopathy2

Polymorphic ventricular1

Electrophysiology3

Phenotype4

HERG4

Nav1.51

Phenotypes4

Calcium15

Sodium channels1

Risk of sudden cardi1

LQTS3

Diseases5

Cardiomyopathy1

Arrest2

Humans3

Abnormalities2

Clinical2

Patients3

Functional5

Encodes1

LQT32

Heterogeneous1

Subunits3

Rhythm2

Myocardium1

Tachyarrhythmias1

Normal cardiac1

CPVT2

Pore2

Mechanisms2

Depolarization2

Syndrome3

Autosomal2

Centre1

Function6

Disease4

Amino1

Molecular1

Membrane1

Anatomical1