Functional modulation of the transient outward current Ito by KCNE beta-subunits and regional distribution in human non-failing and failing hearts

Objectives: The function of Kv4.3 (KCND3) channels, which underlie the transient outward current I,, in human heart, can be modulated by several accessory subunits such as KChIP2 and KCNE1-KCNE5. Here we aimed to determine the regional expression of Kv4.3, KChIP2, and KCNE mRNAs in non-failing and failing human hearts and to investigate the functional consequences of subunit coexpression in heterologous expression systems. Methods: We quantified mRNA levels for two Kv4.3 isoforms, Kv4.3-S and Kv4.3-L, and for KChIP2 as well as KCNE1-KCNE5 with real-time RT-PCR. We also studied the effects of KCNEs on Kv4.3 + KChIP2 current characteristics in CHO cells with the whole-cell voltage-clamp method. Results: In non-failing hearts, low expression was found for KCNE1, KCNE3, and KCNE5, three times higher expression for KCNE2, and 60 times higher for KCNE4. Transmural gradients were detected only for KChIP2 in left and right ventricles. Compared to non-failing tissue, failing hearts showed higher expression of Kv4.3-L and KCNE1 and lower of Kv4.3-S, KChIP2, KCNE4, and KCNE5. In CHO cells, Kv4.3 + KChIP2 currents were differentially modified by co-expressed KCNEs: time constants of inactivation were shorter with KCNE1 and KCNE3-5 while time-to-peak was decreased, and V-0.5 of steady-state inactivation was shifted to more negative potentials by all KCNE subunits. Importantly, KCNE2 induced a unique and prominent 'overshoot' of peak current during recovery from inactivation similar to that described for human I-to while other KCNE subunits induced little (KCNE4,5) or no overshoot. Conclusions: All KCNEs are expressed in the human heart at the transcript level. Compared to It. in native human myocytes, none of the combination of KChIP2 and KCNE produced an ideal congruency in current characteristics, suggesting that additional factors contribute to the regulation of the native I-to channel

The G protein-gated potassium current I(K,ACh) is constitutively active in patients with chronic atrial fibrillation

Background— The molecular mechanism of increased background inward rectifier current (IK1) in atrial fibrillation (AF) is not fully understood. We tested whether constitutively active acetylcholine (ACh)-activated IK,ACh contributes to enhanced basal conductance in chronic AF (cAF). Methods and Results— Whole-cell and single-channel currents were measured with standard voltage-clamp techniques in atrial myocytes from patients with sinus rhythm (SR) and cAF. The selective IK,ACh blocker tertiapin was used for inhibition of IK,ACh. Whole-cell basal current was larger in cAF than in SR, whereas carbachol (CCh)-activated IK,ACh was lower in cAF than in SR. Tertiapin (0.1 to 100 nmol/L) reduced IK,ACh in a concentration-dependent manner with greater potency in cAF than in SR (−logIC50: 9.1 versus 8.2; P<0.05). Basal current contained a tertiapin-sensitive component that was larger in cAF than in SR (tertiapin [10 nmol/L]-sensitive current at −100 mV: cAF, −6.7±1.2 pA/pF, n=16/5 [myocytes/patients] versus SR, −1.7±0.5 pA/pF, n=24/8), suggesting contribution of constitutively active IK,ACh to basal current. In single-channel recordings, constitutively active IK,ACh was prominent in cAF but not in SR (channel open probability: cAF, 5.4±0.7%, n=19/9 versus SR, 0.1±0.05%, n=16/9; P<0.05). Moreover, IK1 channel open probability was higher in cAF than in SR (13.4±0.4%, n=19/9 versus 11.4±0.7%, n=16/9; P<0.05) without changes in other channel characteristics. Conclusions— Our results demonstrate that larger basal inward rectifier K+ current in cAF consists of increased IK1 activity and constitutively active IK,ACh. Blockade of IK,ACh may represent a new therapeutic target in AF

Transport and thermoelectric properties of the LaAlO3_3/SrTiO3_3 interface

The transport and thermoelectric properties of the interface between SrTiO$_3$ and a 26-monolayer thick LaAlO$_3$-layer grown at high oxygen-pressure have been investigated at temperatures from 4.2 K to 100 K and in magnetic fields up to 18 T. For $T>$ 4.2 K, two different electron-like charge carriers originating from two electron channels which contribute to transport are observed. We probe the contributions of a degenerate and a non-degenerate band to the thermoelectric power and develop a consistent model to describe the temperature dependence of the thermoelectric tensor. Anomalies in the data point to an additional magnetic field dependent scattering.Comment: 7 pages, 4 figure

Magneto Seebeck effect in REFeAsO (RE=rare earth) compounds: probing the magnon drag scenario

We investigate Seebeck effect in REFeAsO (RE=rare earth)compounds as a function of temperature and magnetic field up to 30T. The Seebeck curves are characterized by a broad negative bump around 50K, which is sample dependent and strongly enhanced by the application of a magnetic field. A model for the temperature and field dependence of the magnon drag contribution to the Seebeck effect by antiferromagnetic (AFM) spin fluctuation is developed. It accounts for the magnitude and scaling properties of such bump feature in our experimental data. This analysis allows to extract precious information on the coupling between electrons and AFM spin fluctuations in these parent compound systems, with implications on the pairing mechanism of the related superconducting compounds

Hamiltonian equation of motion and depinning phase transition in two-dimensional magnets

Based on the Hamiltonian equation of motion of the $\phi^4$ theory with quenched disorder, we investigate the depinning phase transition of the domain-wall motion in two-dimensional magnets. With the short-time dynamic approach, we numerically determine the transition field, and the static and dynamic critical exponents. The results show that the fundamental Hamiltonian equation of motion belongs to a universality class very different from those effective equations of motion.Comment: 6 pages, 7 figures, have been accept by EP

Depinning transition and thermal fluctuations in the random-field Ising model

We analyze the depinning transition of a driven interface in the 3d random-field Ising model (RFIM) with quenched disorder by means of Monte Carlo simulations. The interface initially built into the system is perpendicular to the [111]-direction of a simple cubic lattice. We introduce an algorithm which is capable of simulating such an interface independent of the considered dimension and time scale. This algorithm is applied to the 3d-RFIM to study both the depinning transition and the influence of thermal fluctuations on this transition. It turns out that in the RFIM characteristics of the depinning transition depend crucially on the existence of overhangs. Our analysis yields critical exponents of the interface velocity, the correlation length, and the thermal rounding of the transition. We find numerical evidence for a scaling relation for these exponents and the dimension d of the system.Comment: 6 pages, including 9 figures, submitted for publicatio

Tracing uptake and assimilation of NO2 in spruce needles with 13N

For the first time, spruce shoots (Picea abies [L.] Karst.) were fumigated in vivo with 13N-labelled NO2 with the aim of elucidating the mechanism of NO2− trapping in the apoplast of the substomatal cavity. Uptake by the needles could be monitored on-line, and a quantitative analysis of the activity records delivered a deposition velocity in agreement with the common dry deposition estimates and ruled out rapid export processes. A fast extraction procedure was applied which revealed that NO2 did not produce any detectable traces of nitrite. In needles in which the enzymes of nitrate reduction were not induced by prior fumigation with NO2, incorporation of NO2 was partially inhibited as compared to the fully induced shoots which took up and assimilated NO2 as expected from a constant influx. The only labelled inorganic species found in the extracts was nitrate (60%), whereas the rest of the label (40%) was assimilated organic nitrogen.A quantitative analysis of the data shows that the reaction of NO2 in the apoplast yields at least three times more nitrate than nitrite, so that the existing models about the apoplastic trapping reaction, disproportionation or antioxidant scavenging, which both postulate substantial production of nitrite, have to be reconsidere