Late cardiac sodium current can be assessed using automated patch-clamp

The cardiac late Na (+) current is generated by a small fraction of voltage-dependent Na (+) channels that undergo a conformational change to a burst-gating mode, with repeated openings and closures during the action potential (AP) plateau. Its magnitude can be augmented by inactivation-defective mutations, myocardial ischemia, or prolonged exposure to chemical compounds leading to drug-induced (di)-long QT syndrome, and results in an increased susceptibility to cardiac arrhythmias. Using CytoPatch™ 2 automated patch-clamp equipment, we performed whole-cell recordings in HEK293 cells stably expressing human Nav1.5, and measured the late Na (+) component as average current over the last 100 ms of 300 ms depolarizing pulses to -10 mV from a holding potential of -100 mV, with a repetition frequency of 0.33 Hz. Averaged values in different steady-state experimental conditions were further corrected by the subtraction of current average during the application of tetrodotoxin (TTX) 30 μM. We show that ranolazine at 10 and 30 μM in 3 min applications reduced the late Na (+) current to 75.0 ± 2.7% (mean ± SEM, n = 17) and 58.4 ± 3.5% ( n = 18) of initial levels, respectively, while a 5 min application of veratridine 1 μM resulted in a reversible current increase to 269.1 ± 16.1% ( n = 28) of initial values. Using fluctuation analysis, we observed that ranolazine 30 μM decreased mean open probability p from 0.6 to 0.38 without modifying the number of active channels n, while veratridine 1 μM increased n 2.5-fold without changing p. In human iPSC-derived cardiomyocytes, veratridine 1 μM reversibly increased APD90 2.12 ± 0.41-fold (mean ± SEM, n = 6). This effect is attributable to inactivation removal in Nav1.5 channels, since significant inhibitory effects on hERG current were detected at higher concentrations in hERG-expressing HEK293 cells, with a 28.9 ± 6.0% inhibition (mean ± SD, n = 10) with 50 μM veratridine.

Wenn Roboter uns kuscheln und pflegen

Podium Robotik in der Pflege Leitung: Susanne Brauer, PhD, Paulus-Akademie Zürich Gäste Prof. Dr. Heidrun Becker, Zürcher Hochschule für Angewandte Wissenschaften, Departement Gesundheit Prof. Dr. Susanne Boshammer, Universität Osnabrück, Philosophie Margrit Lüscher, Geschäftsleiterin, Alterszentrum Bruggwiesen Prof. Dr. Pasqualina Perrig-Chiello, Universität Bern, Psychologie Martin Rüfenacht, Manager Healthcare bei CISCO

The European Network for Translational Research in Atrial Fibrillation (EUTRAF): objectives and initial results

Atrial fibrillation (AF) is the most common sustained arrhythmia in the general population. As an age-related arrhythmia AF is becoming a huge socio-economic burden for European healthcare systems. Despite significant progress in our understanding of the pathophysiology of AF, therapeutic strategies for AF have not changed substantially and the major challenges in the management of AF are still unmet. This lack of progress may be related to the multifactorial pathogenesis of atrial remodelling and AF that hampers the identification of causative pathophysiological alterations in individual patients. Also, again new mechanisms have been identified and the relative contribution of these mechanisms still has to be established. In November 2010, the European Union launched the large collaborative project EUTRAF (European Network of Translational Research in Atrial Fibrillation) to address these challenges. The main aims of EUTRAF are to study the main mechanisms of initiation and perpetuation of AF, to identify the molecular alterations underlying atrial remodelling, to develop markers allowing to monitor this processes, and suggest strategies to treat AF based on insights in newly defined disease mechanisms. This article reports on the objectives, the structure, and initial results of this network.

Der Physiologus und das Neue Testament. Die neutestamentlichen Wurzeln der frühchristlichen Naturallegorese

Der Beitrag untersucht die hermeneutische Methode des griechischen Physiologus, die bereits Pitra (1855) in seiner kritischen Edition als Allegorie bzw. Allegorese bezeichnete, und zeigt die neutestamentlichen Wurzeln dieser ersten christlichen Naturallegorese auf. Denn im Physiologus handelt es sich um keine Allegorie im klassischen Sinne, sondern um ihre genuin christliche Form. Diese kennt man zwar vor allem aus den Werken des Klemens von Alexandrien und Origenes, ihre Grundlagen wurden aber schon von Paulus und Johannes im Neuen Testament gelegt. Auch im Physiologus dient der Christus als hermeneutischer Schlüssel, die Stelle des Alten Testamentes nimmt allerdings die ‹Natur› ein, die allegorisch gedeutet und umgeschrieben wird: «So sollen auch die vollkommenen Christenmenschen die Worte des Alten Testamentes vom Geist unterscheiden, damit dich nicht etwa der Buchstabe töte. Denn Paulus hat gesagt: ‹Das Gesetz ist geistlich›» [Physiologus 12, Von der Ameise; Röm 7,14; 2 Kor 3,6].