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. The thresholdless chaotic mechanism considered here is likely to be applicable to other inhomogeneous systems.

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. Indeed, for measured wave amplitudes in the quiet corona, ion orbits are shown to cross quasi-periodically one or several slowly pulsating separatrices in phase space. Now, a separatrix is an orbit with an infinite period, thus much longer than the pulsation one. Therefore, each separatrix crossing cancels adiabatic invariance, and yields a very strong energy transfer from the wave, and thus particle heating. This occurs whatever be the wave spectrum, even a monochromatic one. The proposed mechanism is so efficient that it might lead to a self-organized picture of coronal heating: all Alfvén waves exceeding a threshold are immediately quenched and transfer their energy to the ions.

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.

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. Depending on the statistics of interest, the same dynamical system may be found diffusive or dominated by its Lévy flights.

[Sudden cardiac death: toward the identification of susceptibity genes]. / Mort subite de l'adulte: Peut-on identifier des facteurs de susceptibilité génétiques?

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. Several clinical studies have demonstrated an increased risk for SCD if one family first-degree relative has experienced SCD, suggesting a genetically acquired susceptibility. Discovering the molecular determinant of this genetic susceptibility may demonstrate extreme value to stratify the risk in the community and to guide prevention. The present review analyses state-of-the-heart research conducted in this field and tentatively measure the distance to be covered before large-scale genetic tests are routinely available in clinical practice.

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. However, they also allow for the formation of magnetic islands which induce transport barriers inside the reversal surface.

Dominant electrostatic nature of the reversed field pinch dynamo.

The origin of the dynamo velocity field of the reversed field pinch within the visco-resistive MHD modeling is uncovered. The main component of this field is an electrostatic drift. The corresponding electrostatic field is related to a small charge separation which is consistent with the quasineutrality approximation, and which should be present in real plasmas, too. While quite natural in the stationary single helicity state, this analysis is shown to extend also to the nonstationary multiple helicity regime. Numerical simulations provide the spatial distribution of fields and of charge separation.

Experimental observation of nonlinear synchronization due to a single wave.

A test electron beam is propagated in a specially designed traveling wave tube. It interacts with a nonresonant wave, and its energy distribution is recorded at the tube output. We report the direct experimental observation of the spatially periodic electron velocity bunching, and of a nonlinear effect on the electron velocity modulation: the synchronization of the particles with the wave responsible for Landau damping in plasma physics. The results are explained by second order perturbation theory in the wave amplitude.

Human Kv1.6 current displays a C-type-like inactivation when re-expressed in cos-7 cells.

The human Kv1.6K(+) channel was functionally re-expressed in COS-7 cells at different levels. Voltage-activated K(+) currents are recorded upon cell membrane depolarization independently of the level of Kv1.6 expression. The current acquires a fast inactivation when Kv1.6 expression is increased. Inactivation was not affected by divalent cations or by extracellular tetraethylammonium. We have characterized the inactivation properties in biophysical terms. The fraction of inactivated current and the kinetics of inactivation are increased as the cell becomes more depolarized. Inactivated current can be reactivated according to a bi-exponential function of time. Additional experiments indicate that Kv1.6 inactivation properties are close to those of a conventional C-type inactivation. This work suggests that the concentration of Kv1.6 channel in the cell membrane strongly modulates the kinetic properties of Kv1.6-induced K(+) current. The physiological implications of these modifications are discussed.

Phosphatidylinositol-4,5-bisphosphate, PIP2, controls KCNQ1/KCNE1 voltage-gated potassium channels: a functional homology between voltage-gated and inward rectifier K+ channels.

Phosphatidylinositol-4,5-bisphosphate (PIP(2)) is a major signaling molecule implicated in the regulation of various ion transporters and channels. Here we show that PIP(2) and intracellular MgATP control the activity of the KCNQ1/KCNE1 potassium channel complex. In excised patch-clamp recordings, the KCNQ1/KCNE1 current decreased spontaneously with time. This rundown was markedly slowed by cytosolic application of PIP(2) and fully prevented by application of PIP(2) plus MgATP. PIP(2)-dependent rundown was accompanied by acceleration in the current deactivation kinetics, whereas the MgATP-dependent rundown was not. Cytosolic application of PIP(2) slowed deactivation kinetics and also shifted the voltage dependency of the channel activation toward negative potentials. Complex changes in the current characteristics induced by membrane PIP(2) was fully restituted by a model originally elaborated for ATP-regulated two transmembrane-domain potassium channels. The model is consistent with stabilization by PIP(2) of KCNQ1/KCNE1 channels in the open state. Our data suggest a striking functional homology between a six transmembrane-domain voltage-gated channel and a two transmembrane-domain ATP-gated channel.

Novel SCN5A mutation leading either to isolated cardiac conduction defect or Brugada syndrome in a large French family.

BACKGROUND: The SCN5A gene encoding the human cardiac sodium channel alpha subunit plays a key role in cardiac electrophysiology. Mutations in SCN5A lead to a large spectrum of phenotypes, including long-QT syndrome, Brugada syndrome, and isolated progressive cardiac conduction defect (Lenègre disease). METHODS AND RESULTS: In the present study, we report the identification of a novel single SCN5A missense mutation causing either Brugada syndrome or an isolated cardiac conduction defect in the same family. A G-to-T mutation at position 4372 was identified by direct sequencing and was predicted to change a glycine for an arginine (G1406R) between the DIII-S5 and DIII-S6 domain of the sodium channel protein. Among 45 family members, 13 were carrying the G1406R SCN5A mutation. Four individuals from 2 family collateral branches showed typical Brugada phenotypes, including ST-segment elevation in the right precordial leads and right bundle branch block. One symptomatic patient with the Brugada phenotype required implantation of a cardioverter-defibrillator. Seven individuals from 3 other family collateral branches had isolated cardiac conduction defects but no Brugada phenotype. Three flecainide test were negative. One patient with an isolated cardiac conduction defect had an episode of syncope and required pacemaker implantation. An expression study of the G1406R-mutated SCN5A showed no detectable Na(+) current but normal protein trafficking. CONCLUSIONS: We conclude that the same mutation in the SCN5A gene can lead either to Brugada syndrome or to an isolated cardiac conduction defect. Our findings suggest that modifier gene(s) may influence the phenotypic consequences of a SCN5A mutation.

Genetic manipulation of cardiac K(+) channel function in mice: what have we learned, and where do we go from here?

In the mammalian myocardium, potassium (K(+)) channels control resting potentials, action potential waveforms, automaticity, and refractory periods and, in most cardiac cells, multiple types of K(+) channels that subserve these functions are expressed. Molecular cloning has revealed the presence of a large number of K(+) channel pore forming (alpha) and accessory (beta) subunits in the heart, and considerable progress has been made recently in defining the relationships between expressed K(+) channel subunits and functional cardiac K(+) channels. To date, more than 20 mouse models with altered K(+) channel expression/functioning have been generated using dominant-negative transgenic and targeted gene deletion approaches. In several instances, the genetic manipulation of K(+) channel subunit expression has revealed the role of specific K(+) channel subunit subfamilies or individual K(+) channel subunit genes in the generation of myocardial K(+) channels. In other cases, however, the phenotypic consequences have been unexpected. This review summarizes what has been learned from the in situ genetic manipulation of cardiac K(+) channel functioning in the mouse, discusses the limitations of the models developed to date, and explores the likely directions of future research.

Gastrointestinal prokinetic drugs have different affinity for the human cardiac human ether-à-gogo K(+) channel.

Agonists of the serotonin 5-hydroxytryptamine 4 (5-HT4) receptor are widely used to activate motility in the gastrointestinal tract. Among these, cisapride was recently withdrawn from the U.S. market because of its proarrhythmic effects. Cisapride is a potent blocker of human ether-à-gogo (HERG) K(+) channels and prolongs the cardiac action potential in a reverse use dependence manner. We compared the effects of four different 5-HT4 receptor agonists (cisapride, prucalopride, renzapride and mosapride) on cloned HERG channels with the objective to evaluate and compare their proarrhythmic potential. K(+) currents from HERG-transfected COS-7 cells were recorded under physiological conditions using the whole cell configuration of the patch-clamp technique. Short (500 ms) depolarizing prepulses were used and following deactivating HERG currents were measured. Cisapride inhibited the HERG channels in a concentration-dependent manner with an IC(50) of 2.4 10(-7) M. The IC(50) value for prucalopride to block HERG (5.7 10(-6) M) was 20-fold higher than that of cisapride. Renzapride was slightly more potent than prucalopride (IC(50) = 1.8 10(-6) M). Mosapride produced no significant effects on the recombinant HERG current. The voltage dependence of HERG block was also investigated. The block mediated by cisapride or renzapride was voltage-dependent whereas that produced by prucalopride was not. We conclude that the rank order of potency of 5-HT4 agonists to block HERG is cisapride > renzapride > prucalopride > mosapride. We also conclude that 5-HT4 agonists devoid of side effects on the HERG current such as mosapride can be found as a safe alternative to cisapride.

Divergent expression of delayed rectifier K(+) channel subunits during mouse heart development.

The repolarization phase of the cardiac action potential is dependent on transmembrane K(+) currents. The slow (I(Ks)) and fast (I(Kr)) components of the delayed-rectifier cardiac K(+) current are generated by pore-forming alpha subunits KCNQ1 and KCNH2, respectively, in association with regulatory beta-subunit KCNE1, KCNE2 and perphaps KCNE3. In the present study we have investigated the distribution of transcripts encoding these five potassium channel-forming subunits during mouse heart development as well as the protein distribution of KCNQ1 and KCNH2. KCNQ1 and KCNH2 mRNAs (and protein) are first expressed at embryonic day (E) 9.5, showing comparable levels of expression within the atrial and ventricular myocardium during the embryonic and fetal stages. In contrast, the beta-subunits display a more dynamic pattern of expression during development. KCNE1 expression is first observed at E9.5 throughout the entire myocardium and progressively is confined to the ventricular myocardium. With further development (E16.5), KCNE1 expression is mainly confined to the compact ventricular myocardium. KCNE2 is first expressed at E9.5 and it is restricted already to the atrial myocardium. KCNE3 is first expressed at E8.5 throughout the myocardium and with further development, it becomes restricted to the atrial myocardium. The fact that alpha subunits are homogeneously distributed within the myocardium, whereas the beta subunits display a regionalized expression profile during cardiac development, suggest that differences in the slow and fast component of the delayed-rectifier cardiac K(+) currents between the atrial and the ventricular cardiomyocytes are mainly determined by differential beta-subunit distribution.

Inactivating properties of recombinant ROMK2 channels expressed in mammalian cells.

Biophysical properties of ROMK2 channel were investigated at physiological temperature, after reexpression of the recombinant ROMK2 protein in a mammalian cell expression system (COS-7). We observed that ROMK2 induced an inwardly rectifying K(+) current whether polyvalent cations were present or not. Above +10 mV, ROMK2-induced current exhibited a voltage- and time-dependent decay, consistent with an inactivation process. Inactivation of ROMK2-induced current was also seen in inside out patch from ROMK2-expressing Xenopus oocyte. In COS-7 cells, inactivation was found to account for most of the inward rectification. Mg(2+) and spermine modulated rectification by accelerating inactivation kinetics independently of membrane potential. These results establish for the first time ROMK2 properties in a mammalian cell expression system.