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[ES] Electrodos nanoestructurados para la estimulación eléctrica de células en cultivo, dispositivos, sistemas y procedimientos asociados. La presente invención se refiere a un electrodo (1) de estimulación eléctrica celular, adaptado para su inserción en una placa (2) miniaturizada con mini-pocillos (3) de cultivo celular, que comprende al menos un material dispuesto como sustrato (4) y un material eléctricamente conductor dispuesto sobre dicho sustrato (4). Ventajosamente, el material eléctricamente conductor está formado por nanopilares (5) metálicos, depositados sobre el sustrato (4) a través de deposición con ángulo de incidencia (GLAD) con pulverización catódica por magnetrón. La invención se refiere, asimismo, a diferentes dispositivos, sistemas, usos y procedimientos asociados a dichos electrodos (1)., [EN] Nanostructured electrodes for the electrical stimulation of cells in culture, devices, systems and associated procedures. The present invention refers to an electrode (1) for cellular electrical stimulation, adapted for insertion in a miniaturized plate (2) with mini-wells (3) for cell culture, comprising at least one material arranged as substrate (4) and an electrically conductive material arranged on said substrate (4). Advantageously, the electrically conductive material is formed by metallic nanopillars (5), deposited on the substrate (4) through deposition with angle of incidence (GLAD) with magnetron sputtering. The invention also refers to different devices, systems, uses and procedures associated with said electrodes (1)., Consejo Superior de Investigaciones Científicas (CSIC), Universidad Autónoma de Madrid; University of Florida Research Foundation, Inc. (UFRF), B2 Patente con examen previo

La presente invención se refiere a un electrodo de estimulación eléctrica celular, adaptado para su inserción en una placa miniaturizada con minipocillos de cultivo celular, que comprende al menos un material eléctricamente conductor dispuesto sobre sustrato. Ventajosamente, el material eléctricamente conductor está formado por nanopilares metálicos, depositados sobre el sustrato a través de deposición con ángulo de incidencia (GLAD) con pulverización catódica por magnetrón. La invención se refiere, asimismo, a diferentes dispositivos, sistemas, usos y procedimiento asociados a dichos electrodos. Peer reviewed Consejo Superior de Investigaciones Científicas (CSIC), Universidad Autónoma de Madrid; University of Florida Research Foundation (UFRF) A1 Solicitud de adición a la patente

Cardiac Nav1.5 and Kir2.1-2.3 channels generate Na (INa) and inward rectifier K (IK1) currents, respectively. The functional INa and IK1 interplay is reinforced by the positive and reciprocal modulation between Nav15 and Kir2.1/2.2 channels to strengthen the control of ventricular excitability. Loss-of-function mutations in the SCN5A gene, which encodes Nav1.5 channels, underlie several inherited arrhythmogenic syndromes, including Brugada syndrome (BrS). We investigated whether the presence of BrS-associated mutations alters IK1 density concomitantly with INa density. Results obtained using mouse models of SCN5A haploinsufficiency, and the overexpression of native and mutated Nav1.5 channels in expression systems - rat ventricular cardiomyocytes and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) - demonstrated that endoplasmic reticulum (ER) trafficking-defective Nav1.5 channels significantly decreased IK1, since they did not positively modulate Kir2.1/2.2 channels. Moreover, Golgi trafficking-defective Nav1.5 mutants produced a dominant negative effect on Kir2.1/2.2 and thus an additional IK1 reduction. Moreover, ER trafficking-defective Nav1.5 channels can be partially rescued by Kir2.1/2.2 channels through an unconventional secretory route that involves Golgi reassembly stacking proteins (GRASPs). Therefore, cardiac excitability would be greatly affected in subjects harboring Nav1.5 mutations with Golgi trafficking defects, since these mutants can concomitantly trap Kir2.1/2.2 channels, thus unexpectedly decreasing IK1 in addition to INa.

International audience; The glycine transporter GLYT1 regulates both glycinergic and glutamatergic neurotransmission by controlling the reuptake of glycine at synapses. Trafficking to the cell surface of GLYT1 is critical for its function. In this article, by using mutational analysis of the GLYT1 C-terminal domain we identified the evolutionary conserved motif R 575}L 576}(X8)D 585} as being necessary for endoplasmic reticulum (ER) export. This is probably due to its capacity to bind Sec24D, a component of the COPII complex. This ER export motif was active when introduced into the related GLYT2 transporter but not in the unrelated VSVG protein. GLYT1 protein in which this motif was mutated was not transported to the plasma membrane, although this effect was rescued by co-expressing these mutants with wild-type GLYT1. This behavior suggests that GLYT1 might form oligomers along the trafficking pathway. Cross-linking assays performed in rat brain synaptosomes, and Fluorescence Resonance Energy Transfer (FRET) microscopy in living cells confirmed the existence of GLYT1 oligomers. In summary, we have identified a motif involved in the ER exit of GLYT1 and in analyzing the influence of this motif, we have found evidence that oligomerization is important for the trafficking of GLYT1 to the cell surface. Because this motif is conserved in the NSS family, it is possible that this finding could be extrapolated to other related transporters.