Thresholdless stochastic particle heating by a single wave.

Stochastic heating is a well-known mechanism through which magnetized particles may be energized by low-frequency electromagnetic waves. In its simplest version, under spatially homogeneous conditions, it is known to be operative only above a threshold in the normalized wave amplitude, which may be a demanding requisite in actual scenarios, severely restricting its range of applicability. In this paper we show, by numerical simulations supported by inspection of the particle Hamiltonian, that allowing for even a very weak spatial inhomogeneity completely removes the threshold, trading the requirement upon the wave amplitude with a requisite upon the duration of the interaction between the wave and particle.

Relevant heating of the quiet solar corona by Alfvén waves: a result of adiabaticity breakdown.

Ion heating by Alfvén waves has been considered for long as the mechanism explaining why the solar corona has a temperature several orders of magnitude higher than the photosphere. Unfortunately, as the measured wave frequencies are much smaller than the ion cyclotron frequency, particles were expected to behave adiabatically, impeding a direct wave-particle energy transfer to take place, except through decorrelating stochastic mechanisms related to broadband wave spectra. This paper proposes a new paradigm for this mechanism by showing it is actually much simpler, more general, and very efficient.

Alfvénic propagation: a key to nonlocal effects in magnetized plasmas.

A long-standing puzzle in fusion research comes from experiments where a sudden peripheral electron temperature perturbation is accompanied by an almost simultaneous opposite change in central temperature, in a way incompatible with local transport models. This Letter shows that these experiments and similar ones are fairly well quantitatively reproduced, when induction effects are incorporated in the total plasma response, alongside standard local diffusive transport, as suggested in earlier work [Plasma Phys. Controlled Fusion 54, 124036 (2012).

Experimental-like helical self-organization in reversed-field pinch modeling.

We report the first nonlinear three-dimensional magnetohydrodynamic (MHD) numerical simulations of the reversed-field pinch (RFP) that exhibit a systematic repetition of quasisingle helicity states with the same dominant mode in between reconnection events. This distinctive feature of experimental self-organized helical RFP plasmas is reproduced in MHD simulations at low dissipation by allowing a helical modulation of the plasma magnetic boundary similar to the experimental one. Realistic mode amplitudes and magnetic topology are also found.

Calculation of transport coefficient profiles in modulation experiments as an inverse problem.

The calculation of transport profiles from experimental measurements belongs in the category of inverse problems which are known to come with issues of ill-conditioning or singularity. A reformulation of the calculation, the matricial approach, is proposed for periodically modulated experiments, within the context of the standard advection-diffusion model where these issues are related to the vanishing of the determinant of a 2×2 matrix. This sheds light on the accuracy of calculations with transport codes, and provides a path for a more precise assessment of the profiles and of the related uncertainty.

Vanishing magnetic shear and electron transport barriers in the RFX-mod reversed field pinch.

We define the safety factor q for the helical plasmas of the experiment RFX-mod by accounting for the actual three-dimensional nature of the magnetic flux surfaces. Such a profile is not monotonic but goes through a maximum located in the vicinity of the electron transport barriers measured by a high resolution Thomson scattering diagnostic. Helical states with a single axis obtained in viscoresistive magnetohydrodynamic numerical simulations exhibit similar nonmonotonic q profiles provided that the final states are preceded by a magnetic island phase, like in the experiment.

KCNQ1 channels voltage dependence through a voltage-dependent binding of the S4-S5 linker to the pore domain.

Voltage-dependent potassium (Kv) channels are tetramers of six transmembrane domain (S1-S6) proteins. Crystallographic data demonstrate that the tetrameric pore (S5-S6) is surrounded by four voltage sensor domains (S1-S4). One key question remains: how do voltage sensors (S4) regulate pore gating? Previous mutagenesis data obtained on the Kv channel KCNQ1 highlighted the critical role of specific residues in both the S4-S5 linker (S4S5(L)) and S6 C terminus (S6(T)).

Gender-related differences in ion-channel and transporter subunit expression in non-diseased human hearts.

Gender-related differences in ventricular electrophysiology are known to be important determinants of human arrhythmic risk, but the underlying molecular basis is poorly understood. The present work aims to provide the first detailed analysis of gender-related cardiac ion-channel gene-distribution, based on samples from non-diseased human hearts. By using a high-throughput quantitative approach, we investigated at a genome-scale the expression of 79 genes encoding ion-channel and transporter subunits in epicardial and endocardial tissue samples from non-diseased transplant donors (10 males, 10 females).

Variable Na(v)1.5 protein expression from the wild-type allele correlates with the penetrance of cardiac conduction disease in the Scn5a(+/-) mouse model.

Background: Loss-of-function mutations in SCN5A, the gene encoding Na(v)1.5 Na+ channel, are associated with inherited cardiac conduction defects and Brugada syndrome, which both exhibit variable phenotypic penetrance of conduction defects. We investigated the mechanisms of this heterogeneity in a mouse model with heterozygous targeted disruption of Scn5a (Scn5a(+/-) mice) and compared our results to those obtained in patients with loss-of-function mutations in SCN5A.

Genetically determined differences in sodium current characteristics modulate conduction disease severity in mice with cardiac sodium channelopathy.

Conduction slowing of the electric impulse that drives the heartbeat may evoke lethal cardiac arrhythmias. Mutations in SCN5A, which encodes the pore-forming cardiac sodium channel alpha subunit, are associated with familial arrhythmia syndromes based on conduction slowing. However, disease severity among mutation carriers is highly variable.

Transcriptional profiling of ion channel genes in Brugada syndrome and other right ventricular arrhythmogenic diseases.

Aims: Brugada syndrome is an inherited sudden-death arrhythmia syndrome. Na(+)-current dysfunction is central, but mutations in the SCN5A gene (encoding the cardiac Na(+)-channel Nav1.5) are present in only 20% of probands.

Biological pacemaker engineered by nonviral gene transfer in a mouse model of complete atrioventricular block.

We hypothesized that a nonviral gene delivery of the hyperpolarization-activated HCN2 channel combined with the beta(2)-adrenergic receptor (ADRB2) would generate a functional pacemaker in a mouse model of complete atrioventricular block (CAVB) induced by radiofrequency ablation of the His bundle. Plasmids encoding HCN2 and ADRB2 mixed with tetronic 304, a poloxamine block copolymer, were injected in the left ventricular free wall (HCN2-ADRB2 mice). Sham mice received a noncoding plasmid.

Sodium channel β1 subunit mutations associated with Brugada syndrome and cardiac conduction disease in humans.

Brugada syndrome is a genetic disease associated with sudden cardiac death that is characterized by ventricular fibrillation and right precordial ST segment elevation on ECG. Loss-of-function mutations in SCN5A, which encodes the predominant cardiac sodium channel alpha subunit NaV1.5, can cause Brugada syndrome and cardiac conduction disease.

IKs response to protein kinase A-dependent KCNQ1 phosphorylation requires direct interaction with microtubules.

Aims: KCNQ1 (alias KvLQT1 or Kv7.1) and KCNE1 (alias IsK or minK) co-assemble to form the voltage-activated K(+) channel responsible for I(Ks)-a major repolarizing current in the human heart-and their dysfunction promotes cardiac arrhythmias. The channel is a component of larger macromolecular complexes containing known and undefined regulatory proteins.

When can the Fokker-Planck equation describe anomalous or chaotic transport?

The Fokker-Planck equation, applied to transport processes in fusion plasmas, can model several anomalous features, including uphill transport, scaling of confinement time with system size, and convective propagation of externally induced perturbations. It can be justified for generic particle transport provided that there is enough randomness in the Hamiltonian describing the dynamics. Then, except for 1 degree of freedom, the two transport coefficients are largely independent.

Regional and tissue specific transcript signatures of ion channel genes in the non-diseased human heart.

The various cardiac regions have specific action potential properties appropriate to their electrical specialization, resulting from a specific pattern of ion-channel functional expression. The present study addressed regionally defined differential ion-channel expression in the non-diseased human heart with a genomic approach. High-throughput real-time RT-PCR was used to quantify the expression patterns of 79 ion-channel subunit transcripts and related genes in atria, ventricular epicardium and endocardium, and Purkinje fibres isolated from 15 non-diseased human donor hearts.

Defining the cellular phenotype of "ankyrin-B syndrome" variants: human ANK2 variants associated with clinical phenotypes display a spectrum of activities in cardiomyocytes.

Background: Mutations in the ankyrin-B gene (ANK2) cause type 4 long-QT syndrome and have been described in kindreds with other arrhythmias. The frequency of ANK2 variants in large populations and molecular mechanisms underlying the variability in the clinical phenotypes are not established. More importantly, there is no cellular explanation for the range of severity of cardiac phenotypes associated with specific ANK2 variants.

[Sudden cardiac death: toward the identification of susceptibity genes].

Sudden cardiac death (SCD) remains a major health problem in developed countries with a rate of incidence close to 1/1000 inhabitants/year. In most cases (>80%), SCD occurs as the initial manifestation of a previously ignored cardiac disease, usually coronary artery disease. As a consequence, known risk factors for SCD overlap with those for coronary artery disease and thus are not contributive to identify individuals prone to SCD in the general population.

The N-terminal juxtamembranous domain of KCNQ1 is critical for channel surface expression: implications in the Romano-Ward LQT1 syndrome.

N-terminal mutations in the KCNQ1 channel are frequently linked to fatal arrhythmias in newborn children and adolescents but the cellular mechanisms involved in this dramatic issue remain, however, to be discovered. Here, we analyzed the trafficking of a series of N-terminal truncation mutants and identified a critical trafficking motif of KCNQ1. This determinant is located in the juxtamembranous region preceding the first transmembrane domain of the protein.

KCNQ1 K+ channel-mediated cardiac channelopathies.

KCNQ1 is a voltage-activated potassium channel alpha-subunit expressed in various cell types, including cardiac myocytes and epithelial cells. KCNQ1 associates with different beta-subunits of the KCNE protein family. In the human heart, KCNQ1 associates with KCNE1 to generate the IKs current characterized by its slow activation and deactivation kinetics.

14-3-3 is a regulator of the cardiac voltage-gated sodium channel Nav1.5.

The voltage-sensitive Na(+) channel Na(v)1.5 plays a crucial role in generating and propagating the cardiac action potential and its dysfunction promotes cardiac arrhythmias. The channel takes part into a large molecular complex containing regulatory proteins.

Bradycardia and slowing of the atrioventricular conduction in mice lacking CaV3.1/alpha1G T-type calcium channels.

The generation of the mammalian heartbeat is a complex and vital function requiring multiple and coordinated ionic channel activities. The functional role of low-voltage activated (LVA) T-type calcium channels in the pacemaker activity of the sinoatrial node (SAN) is, to date, unresolved. Here we show that disruption of the gene coding for CaV3.

Progressive cardiac conduction defect is the prevailing phenotype in carriers of a Brugada syndrome SCN5A mutation.

Introduction: Loss-of-function mutations in the SCN5A gene encoding the cardiac sodium channel are responsible for Brugada syndrome (BS) and also for progressive cardiac conduction disease (inherited Lenègre disease). In an attempt to clarify the frontier between these two entities, we have characterized cardiac conduction defect and its evolution with aging in a cohort of 78 patients carrying a SCN5A mutation linked to Brugada syndrome.

Methods And Results: Families were included in the study if a SCN5A mutation was identified in a BS proband and if at least two family members were mutation carriers.

Transport barrier inside the reversal surface in the chaotic regime of the reversed-field pinch.

Magnetic field lines and the corresponding particle orbits are computed for a typical chaotic magnetic field provided by a magnetohydrodynamics numerical simulation of the reversed-field pinch. The m = 1 modes are phase locked and produce a toroidally localized bulging of the plasma which increases particle transport. The m = 0 and m = 1 modes produce magnetic chaos implying poor confinement.