Norbert Nagy

Ionic mechanisms limiting cardiac repolarization reserve in humans compared to dogs.

•  Cardiac repolarization, through which heart‐cells return to their resting state after having fired, is a delicate process, susceptible to disruption by common drugs and clinical conditions. •  Animal models, particularly the dog, are often used to study repolarization properties and responses to drugs, with the assumption that such findings are relevant to humans. However, little is known about the applicability of findings in animals to man. •  Here, we studied the contribution of various ion‐currents to cardiac repolarization in canine and human ventricle. •  Humans showed much greater repolarization‐impairing effects of drugs blocking the rapid delayed‐rectifier current IKr than dogs, because of lower repolarization‐reserve contributions from two other important repolarizing currents (the inward‐rectifier IK1 and slow delayed‐rectifier IKs). •  Our findings clarify differences in cardiac repolarization‐processes among species, highlighting the importance of caution when extrapolating results from animal models to man.

Large area self-assembled masking for photonic applications

Ordered porous structures for photonic application were fabricated on p- and n-type silicon by means of masking against ion implantation with Langmuir-Blodgett (LB) films. LB films from Stober silica spheres [J. Colloid Interface Sci. 26, 62 (1968)] of 350nm diameter were applied in the boron and phosphorus ion-implantation step, thereby offering a laterally periodic doping pattern. Ordered porous silicon structures were obtained after performing an anodic etch and were then removed by alkaline etching resulting in the required two-dimensional photonic arrangement. The LB silica masks and the resulting silicon structures were studied by field emission scanning electron microscope analysis.

ORM‐10103, a novel specific inhibitor of the Na+/Ca2+ exchanger, decreases early and delayed afterdepolarizations in the canine heart

At present there are no small molecule inhibitors that show strong selectivity for the Na+/Ca2+ exchanger (NCX). Hence, we studied the electrophysiological effects of acute administration of ORM‐10103, a new NCX inhibitor, on the NCX and L‐type Ca2+ currents and on the formation of early and delayed afterdepolarizations.

Na+/Ca2+ exchanger inhibition exerts a positive inotropic effect in the rat heart, but fails to influence the contractility of the rabbit heart

Background and purpose: The Na+/Ca2+ exchanger (NCX) may play a key role in myocardial contractility. The operation of the NCX is affected by the action potential (AP) configuration and the intracellular Na+ concentration. This study examined the effect of selective NCX inhibition by 0.1, 0.3 and 1.0 μM SEA0400 on the myocardial contractility in the setting of different AP configurations and different intracellular Na+ concentrations in rabbit and rat hearts.

The Na+/Ca2+ exchange blocker SEA0400 fails to enhance cytosolic Ca2+ transient and contractility in canine ventricular cardiomyocytes

AIMS This study was designed to evaluate the effects of the Na(+)/Ca(2+) exchange (NCX) inhibitor SEA0400 on Ca(2+) handling in isolated canine ventricular myocytes. METHODS AND RESULTS Intracellular Ca(2+) ([Ca(2+)](i)) transients, induced by either field stimulation or caffeine flush, were monitored using Ca(2+) indicator dyes. [Ca(2+)](i)-dependent modulation of the inhibitory effect of SEA0400 on NCX was characterized by the changes in Ni(2+)-sensitive current in voltage-clamped myocytes. Sarcoplasmic reticulum (SR) Ca(2+) release and uptake were studied in SR membrane vesicles. Gating properties of single-ryanodine receptors were analysed in lipid bilayers. Ca(2+) sensitivity of the contractile machinery was evaluated in chemically skinned myocytes. In myocytes paced at 1 Hz, neither diastolic [Ca(2+)](i) nor the amplitude of [Ca(2+)](i) transients was significantly altered by SEA0400 up to the concentration of 1 microM, which was shown to inhibit the exchange current. The blocking effect of SEA0400 on NCX decreased with increasing [Ca(2+)](i), and it was more pronounced in reverse than in forward mode operation at every [Ca(2+)](i) examined. The rate of decay of the caffeine-induced [Ca(2+)](i) transients was decreased significantly by 1 microM SEA0400; however, this effect was only a fraction of that observed with 10 mM NiCl(2). Neither SR Ca(2+) release and uptake nor cell shortening and Ca(2+) sensitivity of the contractile proteins were influenced by SEA0400. CONCLUSION The lack of any major SEA0400-induced shift in Ca(2+) transients or contractility of myocytes can well be explained by its limited inhibitory effect on NCX (further attenuated by elevated [Ca(2+)](i) levels) and a concomitant reduction in Ca(2+) influx due to the predominantly reverse mode blockade of NCX and suppression of L-type Ca(2+) current.

Controlling the nanoscale rippling of graphene with SiO2 nanoparticles

The electronic properties of graphene can be significantly influenced by mechanical strain. One practical approach to induce strain in graphene is to transfer atomically thin membranes onto pre-patterned substrates with specific corrugations. The possibility of using nanoparticles to impart extrinsic rippling to graphene has not been fully explored yet. Here we study the structure and elastic properties of graphene grown by chemical vapour deposition and transferred onto a continuous layer of SiO2 nanoparticles with diameters of around 25 nm, prepared on a Si substrate by the Langmuir-Blodgett technique. We show that the corrugation of the transferred graphene, and thus the membrane strain, can be modified by annealing at moderate temperatures. The membrane parts bridging the nanoparticles are suspended and can be reversibly lifted by the attractive forces between an atomic force microscope tip and graphene. This allows the dynamic control of the local morphology of graphene nanomembranes.

Selective Na+/Ca2+ exchanger inhibition prevents Ca2+ overload‐induced triggered arrhythmias

Augmented Na+/Ca2+ exchanger (NCX) activity may play a crucial role in cardiac arrhythmogenesis; however, data regarding the anti‐arrhythmic efficacy of NCX inhibition are debatable. Feasible explanations could be the unsatisfactory selectivity of NCX inhibitors and/or the dependence of the experimental model on the degree of Ca2+i overload. Hence, we used NCX inhibitors SEA0400 and the more selective ORM10103 to evaluate the efficacy of NCX inhibition against arrhythmogenic Ca2+i rise in conditions when [Ca2+]i was augmented via activation of the late sodium current (INaL) or inhibition of the Na+/K+ pump.

Antibacterial properties of Ag-TiO2 composite sol-gel coatings

In this work the long-term antibacterial activity of silver doped titania coatings is studied systematically as a function of the titania layer structure (with and without molecular template) and the amount and physical properties of the silver dopant. Silver was incorporated in two different ways into the titania sol–gel films, either by co-deposition, i.e., adding the silver ions directly to the precursor sol of the layer or by post-synthetic impregnation of the mesoporous titania coating. The structure and morphology of the layers were investigated using transmission and scanning electron microscopy, whereas the silver content was determined by Rutherford backscattering spectrometry. Antibacterial properties against Escherichia coli bacteria were studied by colony forming unit assay and agar diffusion method. It was found that directly after preparation, all composite coatings show antibacterial activity both in the dark and under visible light illumination. The antibacterial activity of the co-deposited samples vanished after the first use despite their high and constant remaining silver content (2.597 at%). This type of coating was not effective in agar diffusion tests at all. The antibacterial activity of the impregnated coatings with lower silver contents (0.596 at% and 1.961 at%), however, showed long-lasting antibacterial effect both in the colony forming unit assay and in agar diffusion tests as well. This can be attributed to the fact that the silver content is distributed over the mesoporous network of the titania coating and is effective during the long-term tests.

Arbitrary tip orientation in STM simulations: 3D WKB theory and application to W(110)

We extend the orbital-dependent electron tunnelling model implemented within the three-dimensional (3D) Wentzel-Kramers-Brillouin (WKB) atom-superposition approach for simulating scanning tunnelling microscopy (STM) by including arbitrary tip orientations. The orientation of the tip is characterized by a local coordinate system centred on the tip apex atom obtained by a rotation with respect to the sample coordinate system. The rotation is described by the Euler angles. Applying our method, we highlight the role of the real-space shape of the electron orbitals involved in the tunnelling, and analyse the convergence and the orbital contributions of the tunnelling current above the W(110) surface depending on the orientation of a model tungsten tip. We also simulate STM images at constant-current condition, and find that their quality depends very much on the tip orientation. Some orientations result in protrusions on the images that do not occur above W atoms. The presence of such apparent atom positions makes it difficult to identify the exact position of surface atoms. It is suggested that this tip orientation effect should be considered in the evaluation of experimental STM images on other surfaces as well. The presented computationally efficient tunnelling model could prove to be useful for obtaining more information on the local tip geometry and orientation by comparing STM experiments to a large number of simulations with systematically varied tip orientations.

Herpesvirus-mediated delivery of a genetically encoded fluorescent ca 2+ sensor to canine cardiomyocytes

We report the development and application of a pseudorabies virus-based system for delivery of troponeon, a fluorescent Ca2+ sensor to adult canine cardiomyocytes. The efficacy of transduction was assessed by calculating the ratio of fluorescently labelled and nonlabelled cells in cell culture. Interaction of the virus vector with electrophysiological properties of cardiomyocytes was evaluated by the analysis of transient outward current (Ito), kinetics of the intracellular Ca2+ transients, and cell shortening. Functionality of transferred troponeon was verified by FRET analysis. We demonstrated that the transfer efficiency of troponeon to cultured adult cardiac myocytes was virtually 100%. We showed that even after four days neither the amplitude nor the kinetics of the Ito current was significantly changed and no major shifts occurred in parameters of [Ca2+]i transients. Furthermore, we demonstrated that infection of cardiomyocytes with the virus did not affect the morphology, viability, and physiological attributes of cells.