New approaches for the identification of KChIP2 ligands to study the KV4.3 channelosome in atrial fibrillati

Resumen del trabajo presentado en el VIII Congreso Red Española de Canales iónico, celebrado en Alicante (España) del 24 al 27 de mayo de 2022.Ion channels are macromolecular complexes present in the plasma membrane and in intracellular organelles of the cells, where they play important functions. The dysfunction of these channels results in several disorders named channelopathies, which represent a challenge for study and treatment.[1] We are focused on voltage-gated potassium channels, specifically on KV4.3. Kv4.3 is expressed in smooth muscle, heart and brain. Within the heart, Kv4.3 channels generate the transient outward potassium current (ITO). However, ITO characteristics are only observed when Kv4.3 assemble with accessory subunits as KChIP2 and DPP6. KV4.3 channelosome play a key role in atrial fibrillation (AF),the most common cardiac arrhythmia, with an estimated prevalence in the general population of 1.5–2%. However, current antiarrhythmic drugs for AF prevention have limited efficacy and considerable potential for adverse effects.[2] KChIP2 (Potassium Channel Interacting Protein 2) belongs to the calcium binding protein superfamily. It is the KChIP member predominantly expressed in heart and a key regulator of cardiac action potential duration. The identification of novel KChIP2 ligands could be useful to understand the role of KV4.3 channelosome in AF and it could help to discover new treatments for AF. [3] In this regard, structure-based virtual screening could be an important tool to accelerate the identification of novel KChIP2 ligands. In this communication, we will describe a multidisciplinary approach that, starting with a structurebased virtual screening, followed by an iterative process of synthesis/biological evaluation/docking studies, has led to the identification of new KChIP2 ligands.PID2019-104366RB-C21, PID2019-104366RB-C22, PID2020-114256RB-I00 and PID2020-119805RB-I00 grants funded by MCIN/AEI/10.13039/501100011033; and PIE202180E073 and 2019AEP148 funded by CSIC. C.V.B. holds PRE2020-093542 FPI grant funded by MCIN/AEI/10.13039/501100011033. PGS was recipient of an FPU grant (FPU17/02731). AB-B holds BES-2017-080184 FPI grant and A.P-L.holds RYC2018-023837-I grant both funded by MCIN/ AEI/ 10.13039/501100011033 and by “ESF Investing in your future

New approaches for the identification of KChIP2 ligands to study the KV4.3 channelosome in atrial fibrillati

Resumen del trabajo presentado en el VIII Congreso Red Española de Canales iónico, celebrado en Alicante (España) del 24 al 27 de mayo de 2022.Ion channels are macromolecular complexes present in the plasma membrane and in intracellular organelles of the cells, where they play important functions. The dysfunction of these channels results in several disorders named channelopathies, which represent a challenge for study and treatment.[1] We are focused on voltage-gated potassium channels, specifically on KV4.3. Kv4.3 is expressed in smooth muscle, heart and brain. Within the heart, Kv4.3 channels generate the transient outward potassium current (ITO). However, ITO characteristics are only observed when Kv4.3 assemble with accessory subunits as KChIP2 and DPP6. KV4.3 channelosome play a key role in atrial fibrillation (AF),the most common cardiac arrhythmia, with an estimated prevalence in the general population of 1.5–2%. However, current antiarrhythmic drugs for AF prevention have limited efficacy and considerable potential for adverse effects.[2] KChIP2 (Potassium Channel Interacting Protein 2) belongs to the calcium binding protein superfamily. It is the KChIP member predominantly expressed in heart and a key regulator of cardiac action potential duration. The identification of novel KChIP2 ligands could be useful to understand the role of KV4.3 channelosome in AF and it could help to discover new treatments for AF. [3] In this regard, structure-based virtual screening could be an important tool to accelerate the identification of novel KChIP2 ligands. In this communication, we will describe a multidisciplinary approach that, starting with a structurebased virtual screening, followed by an iterative process of synthesis/biological evaluation/docking studies, has led to the identification of new KChIP2 ligands.PID2019-104366RB-C21, PID2019-104366RB-C22, PID2020-114256RB-I00 and PID2020-119805RB-I00 grants funded by MCIN/AEI/10.13039/501100011033; and PIE202180E073 and 2019AEP148 funded by CSIC. C.V.B. holds PRE2020-093542 FPI grant funded by MCIN/AEI/10.13039/501100011033. PGS was recipient of an FPU grant (FPU17/02731). AB-B holds BES-2017-080184 FPI grant and A.P-L.holds RYC2018-023837-I grant both funded by MCIN/ AEI/ 10.13039/501100011033 and by “ESF Investing in your future

Spread of a SARS-CoV-2 variant through Europe in the summer of 2020.

Following its emergence in late 2019, the spread of SARS-CoV-21,2 has been tracked by phylogenetic analysis of viral genome sequences in unprecedented detail3–5. Although the virus spread globally in early 2020 before borders closed, intercontinental travel has since been greatly reduced. However, travel within Europe resumed in the summer of 2020. Here we report on a SARS-CoV-2 variant, 20E (EU1), that was identified in Spain in early summer 2020 and subsequently spread across Europe. We find no evidence that this variant has increased transmissibility, but instead demonstrate how rising incidence in Spain, resumption of travel, and lack of effective screening and containment may explain the variant’s success. Despite travel restrictions, we estimate that 20E (EU1) was introduced hundreds of times to European countries by summertime travellers, which is likely to have undermined local efforts to minimize infection with SARS-CoV-2. Our results illustrate how a variant can rapidly become dominant even in the absence of a substantial transmission advantage in favourable epidemiological settings. Genomic surveillance is critical for understanding how travel can affect transmission of SARS-CoV-2, and thus for informing future containment strategies as travel resumes. © 2021, The Author(s), under exclusive licence to Springer Nature Limited

Advancements in non-destructive control of efficiency of electrochemical repair techniques

[EN] The main electrochemical techniques used for reducing corrosion on reinforced structures are cathodic protection (CP), electrochemical chloride extraction (ECE) and realkalisation (ER). Traditionally, for controlling the efficiency of CP, standard methods based in the depolarisation of rebar are used, with inconvenience of requiring the interruption of the protection current even for several hours. Concerning ECE and ER, the usual methods involve extraction and chemical analysis (chloride and hydroxyl ions respectively) of cores from the structure. In this paper, some non-destructive methods for monitoring the performance of the electrochemical repair techniques, are presented and analysed. In CP, a new developed methodology, called passivity verification technique (PVT), which uses the electrochemical impedance spectroscopy concept, is described. This is a fast method that does not require interruption of the cathodic protection current and the results obtained are in agreement with those obtained by standard depolarisation methods. As long as ECE and ER are concerned, the corrosion potential and corrosion rate measured by the polarisation resistance technique are the suggested non-destructive indicators of the efficiency of the technique at the end of the treatment. Additionally, for ER, the detection of a sudden increase in the intensity of electrical current passing, and a parallel establishment of electro-osmotic flux, is also postulated as a key parameter for practical control during the application of the efficiency of the realkalisation. Finally, it is also presented a new parameter 'standardised by the resistance charges (SRC)', which would be a more indicative parameter than simple recording the coulombs to check the efficiency during ECE treatment.Peer reviewe

Efficiency control of electrochemical repair techniques

Trabajo presentado en la 2nd International Conference on Concrete Repair, Rehabilitation and Retrofitting (ICCRRR), celebrada en Cape Town (Sudáfrica), del 24 al 26 de noviembre de 200

Development of pharmacological tools to study the kv4.3 channelosome in atrial fibrillation

Resumen del trabajo presentado en el XX National Meeting of the Spanish Society of Medicinal Chemistry, celebrado en Santiago de Compostela (España) del 19 al 22 de junio de 2022.Ion channels are macromolecular complexes present in the plasma membrane and in intracellular organelles of the cells, where they play important functions, such as smooth muscle contraction or secretion of hormones. The dysfunction of these channels results in several disorders named channelopathies, which represent a challenge for study and treatment.[1] We are focused on voltage-gated potassium channels, specifically on KV4.3 and its role in atrial fibrillation (AF). KV4.3 channel is expressed in smooth muscle, heart and brain. Its activation generates outward currents operating at subthreshold membrane potentials as recorded from myocardial cells (ITO, transient outward current). KV4.3 plays a key role in AF, the most common cardiac arrhythmia, with an estimated prevalence in the general population of 1.5–2%. However, current antiarrhythmic drugs for AF prevention have limited efficacy and considerable potential for adverse effects.[2] To reproduce the ITO currents, KV4.3 channels need to assemble with other subunits, forming channelosome. KChIPs (Potassium Channel Interacting Proteins), which belong to the calcium binding protein superfamily, forms the KV4.3 channelosome, along with other proteins.[3] To study the complex interaction of KV4.3 channelosome and the development of modulators, the interplay of different techniques is central to advance knowledge. In this regard, the development of novel KChIPs modulators and fluorescent biosensors constitutes invaluable pharmacological tools to unravel the KV4 channelosome and its role in AF.[3] In this communication, we will describe preliminary results towards the identification of new pharmacological tools to study the KChIPs/KV4 interaction.This work was supported by the projects: PID2019-104366RB-C21, PID2019-104366RB-C22, PID2020-114256RB-I00 and PID2020-119805RB-I00 funded by MCIN/ AEI /10.13039/501100011033; and the projects PIE202180E073 and 2019AEP148 funded by CSIC. C. Viedma Barba holds the grant PRE2020-093542 and M. Valencia holds the grant PRE2020-093950, both funded by MCIN/AEI/10.13039/501100011033. A. Pérez-Lara holds the grant RYC2018-023837-I funded by MCIN/AEI/10.13039/501100011033 and by “ESF Investing in your future”