Adaption strategies used by siblings to childhood cancer patients.

Objective: Siblings of childhood cancer patients experience social challenges. The results presented in this article are part of a larger qualitative study aiming to generate empirical knowledge about social consequences of childhood cancer from the family's perspective.

Methods: Data were collected through interviews, observational studies, and questionnaires.

Magnetocardiography on an isolated animal heart with a room-temperature optically pumped magnetometer.

Optically pumped magnetometers are becoming a promising alternative to cryogenically-cooled superconducting magnetometers for detecting and imaging biomagnetic fields. Magnetic field detection is a completely non-invasive method, which allows one to study the function of excitable human organs with a sensor placed outside the human body. For instance, magnetometers can be used to detect brain activity or to study the activity of the heart.

Rare truncating variants in the sarcomeric protein titin associate with familial and early-onset atrial fibrillation.

A family history of atrial fibrillation constitutes a substantial risk of developing the disease, however, the pathogenesis of this complex disease is poorly understood. We perform whole-exome sequencing on 24 families with at least three family members diagnosed with atrial fibrillation (AF) and find that titin-truncating variants (TTNtv) are significantly enriched in these patients (P = 1.76 × 10).

Functional consequences of genetic variation in sodium channel modifiers in early onset lone atrial fibrillation.

Aim: We investigated the effect of variants in genes encoding sodium channel modifiers SNTA1 and GPD1L found in early onset atrial fibrillation (AF) patients.

Patients & Methods: Genetic screening in patients with early onset lone AF revealed three variants in GPD1L and SNTA1 in three AF patients. Functional analysis was performed by patch-clamp electrophysiology.

Trafficking of Kv2.1 Channels to the Axon Initial Segment by a Novel Nonconventional Secretory Pathway.

Kv2.1 is a major delayed-rectifier voltage-gated potassium channel widely expressed in neurons of the CNS. Kv2.

Termination of Vernakalant-Resistant Atrial Fibrillation by Inhibition of Small-Conductance Ca-Activated K Channels in Pigs.

Background: Evidence has emerged that small-conductance Ca-activated K (SK) channels constitute a new target for treatment of atrial fibrillation (AF). SK channels are predominantly expressed in the atria as compared with the ventricles. Various marketed antiarrhythmic drugs are limited by ventricular adverse effects and efficacy loss as AF progresses.

Numerous Brugada syndrome-associated genetic variants have no effect on J-point elevation, syncope susceptibility, malignant cardiac arrhythmia, and all-cause mortality.

Purpose: We investigated whether Brugada syndrome (BrS)-associated variants identified in the general population have an effect on J-point elevation as well as whether carriers of BrS variants were more prone to experience syncope and malignant ventricular arrhythmia and had increased mortality compared with noncarriers.

Methods: All BrS-associated variants were identified using the Human Gene Mutation Database (HGMD). Individuals were randomly selected from a general population study using whole-exome sequencing data (n = 870) and genotype array data (n = 6,161) and screened for BrS-associated variants.

Non-invasive detection of animal nerve impulses with an atomic magnetometer operating near quantum limited sensitivity.

Magnetic fields generated by human and animal organs, such as the heart, brain and nervous system carry information useful for biological and medical purposes. These magnetic fields are most commonly detected using cryogenically-cooled superconducting magnetometers. Here we present the first detection of action potentials from an animal nerve using an optical atomic magnetometer.

The two-pore domain potassium channel, TWIK-1, has a role in the regulation of heart rate and atrial size.

The two-pore domain potassium (K(+)) channel TWIK-1 (or K2P1.1) contributes to background K(+) conductance in diverse cell types. TWIK-1, encoded by the KCNK1 gene, is present in the human heart with robust expression in the atria, however its physiological significance is unknown.

Live Imaging of Kv7.2/7.3 Cell Surface Dynamics at the Axon Initial Segment: High Steady-State Stability and Calpain-Dependent Excitotoxic Downregulation Revealed.

Unlabelled: The voltage-gated K(+) channels Kv7.2 and Kv7.3 are located at the axon initial segment (AIS) and exert strong control over action potential generation.

pH-dependent inhibition of K₂P3.1 prolongs atrial refractoriness in whole hearts.

In isolated human atrial cardiomyocytes, inhibition of K2P3.1 K(+) channels results in action potential (action potential duration (APD)) prolongation. It has therefore been postulated that K2P3.

Fundamental role for the KCNE4 ancillary subunit in Kv7.4 regulation of arterial tone.

Key Points: KCNE4 alters the biophysical properties and cellular localization of voltage-gated potassium channel Kv7.4. KCNE4 is expressed in a variety of arteries and, in mesenteric arteries, co-localizes with Kv7.

Protein kinase A stimulates Kv7.1 surface expression by regulating Nedd4-2-dependent endocytic trafficking.

The potassium channel Kv7.1 plays critical physiological roles in both heart and epithelial tissues. In heart, Kv7.

Rare genetic variants previously associated with congenital forms of long QT syndrome have little or no effect on the QT interval.

Aims: We studied whether variants previously associated with congenital long QT syndrome (cLQTS) have an effect on the QTc interval in a Danish population sample. Furthermore, we assessed whether carriers of variants in cLQTS-associated genes are more prone to experience syncope compared with non-carriers and whether carriers have an increased mortality compared with non-carriers.

Methods And Results: All genetic variants previously associated with cLQTS were surveyed using the Human Gene Mutation Database.

Analysis of the Antitumor Activity of Clotrimazole on A375 Human Melanoma Cells.

Aim: The current study was designed to characterize the anticancer effects of clotrimazole on human cutaneous melanoma cells.

Materials And Methods: The v-raf murine sarcoma viral oncogene homolog B1 V600E mutant melanoma cell line A375 was used as an in vitro model. Characterization tools included analyses of cell viability, gene expression, cell-cycle progression, annexin V reactivity and internucleosomal DNA fragmentation.

Preservation of cardiac function by prolonged action potentials in mice deficient of KChIP2.

Inherited ion channelopathies and electrical remodeling in heart disease alter the cardiac action potential with important consequences for excitation-contraction coupling. Potassium channel-interacting protein 2 (KChIP2) is reduced in heart failure and interacts under physiological conditions with both Kv4 to conduct the fast-recovering transient outward K(+) current (Ito,f) and with CaV1.2 to mediate the inward L-type Ca(2+) current (ICa,L).

IKs Gain- and Loss-of-Function in Early-Onset Lone Atrial Fibrillation.

Introduction: Atrial fibrillation (AF) is the most frequent cardiac arrhythmia. The potassium current IKs is essential for cardiac repolarization. Gain-of-function mutation in KCNQ1, the gene encoding the pore-forming α-subunit of the IKs channel (KV 7.

BK channel activators and their therapeutic perspectives.

The large conductance calcium- and voltage-activated K(+) channel (KCa1.1, BK, MaxiK) is ubiquitously expressed in the body, and holds the ability to integrate changes in intracellular calcium and membrane potential. This makes the BK channel an important negative feedback system linking increases in intracellular calcium to outward hyperpolarizing potassium currents.

KCNMA1 encoded cardiac BK channels afford protection against ischemia-reperfusion injury.

Mitochondrial potassium channels have been implicated in myocardial protection mediated through pre-/postconditioning. Compounds that open the Ca2+- and voltage-activated potassium channel of big-conductance (BK) have a pre-conditioning-like effect on survival of cardiomyocytes after ischemia/reperfusion injury. Recently, mitochondrial BK channels (mitoBKs) in cardiomyocytes were implicated as infarct-limiting factors that derive directly from the KCNMA1 gene encoding for canonical BKs usually present at the plasma membrane of cells.

Annotation of loci from genome-wide association studies using tissue-specific quantitative interaction proteomics.

Genome-wide association studies (GWAS) have identified thousands of loci associated with complex traits, but it is challenging to pinpoint causal genes in these loci and to exploit subtle association signals. We used tissue-specific quantitative interaction proteomics to map a network of five genes involved in the Mendelian disorder long QT syndrome (LQTS). We integrated the LQTS network with GWAS loci from the corresponding common complex trait, QT-interval variation, to identify candidate genes that were subsequently confirmed in Xenopus laevis oocytes and zebrafish.

NS19504: a novel BK channel activator with relaxing effect on bladder smooth muscle spontaneous phasic contractions.

Large-conductance Ca(2+)-activated K(+) channels (BK, KCa1.1, MaxiK) are important regulators of urinary bladder function and may be an attractive therapeutic target in bladder disorders. In this study, we established a high-throughput fluorometric imaging plate reader-based screening assay for BK channel activators and identified a small-molecule positive modulator, NS19504 (5-[(4-bromophenyl)methyl]-1,3-thiazol-2-amine), which activated the BK channel with an EC50 value of 11.

Gain-of-function mutations in potassium channel subunit KCNE2 associated with early-onset lone atrial fibrillation.

Aims: Atrial fibrillation (AF) is the most common cardiac arrhythmia. Disturbances in cardiac potassium conductance are considered as one of the disease mechanisms in AF. We aimed to investigate if mutations in potassium-channel β-subunits KCNE2 and KCNE3 are associated with early-onset lone AF.

Cardiac potassium channel subtypes: new roles in repolarization and arrhythmia.

About 10 distinct potassium channels in the heart are involved in shaping the action potential. Some of the K+ channels are primarily responsible for early repolarization, whereas others drive late repolarization and still others are open throughout the cardiac cycle. Three main K+ channels drive the late repolarization of the ventricle with some redundancy, and in atria this repolarization reserve is supplemented by the fairly atrial-specific KV1.

Loss of K+ currents in heart failure is accentuated in KChIP2 deficient mice.

Introduction: KV 4 together with KV Channel-Interacting Protein 2 (KChIP2) mediate the fast recovering transient outward potassium current (I(to,f)) in the heart. KChIP2 is downregulated in human heart failure (HF), potentially underlying the loss of I(to,f). We investigated remodeling associated with HF hypothesizing that KChIP2 plays a central role in the modulation of outward K(+) currents in HF.

Specific sorting and post-Golgi trafficking of dendritic potassium channels in living neurons.

Proper membrane localization of ion channels is essential for the function of neuronal cells. Particularly, the computational ability of dendrites depends on the localization of different ion channels in specific subcompartments. However, the molecular mechanisms that control ion channel localization in distinct dendritic subcompartments are largely unknown.