The expression of the rare caveolin-3 variant T78M alters cardiac ion channels function and membrane excitability
| Autor: | Mirko Baruscotti, Elena Vezzoli, Dario DiFrancesco, Giulia Campostrini, Lia Crotti, Alessio Lissoni, Maura Francolini, Peter J. Schwartz, Claudia Bazzini, Riccardo Cappato, Annalisa Bucchi, Stefano Severi, Matteo Fantini, Mattia Bonzanni, Andrea Barbuti, Ilaria Rivolta, Raffaella Milanesi |
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| Přispěvatelé: | Campostrini, Giulia, Bonzanni, Mattia, Lissoni, Alessio, Bazzini, Claudia, Milanesi, Raffaella, Vezzoli, Elena, Francolini, Maura, Baruscotti, Mirko, Bucchi, Annalisa, Rivolta, Ilaria, Fantini, Matteo, Severi, Stefano, Cappato, Riccardo, Crotti, Lia, Schwartz, Peter J., DiFrancesco, Dario, Barbuti, Andrea, Campostrini, G, Bonzanni, M, Lissoni, A, Bazzini, C, Milanesi, R, Vezzoli, E, Francolini, M, Baruscotti, M, Bucchi, A, Rivolta, I, Fantini, M, Severi, S, Cappato, R, Crotti, L, Schwartz, P, Di Francesco, D, Barbuti, A |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Potassium Channels Caveolin 3 Physiology Caveolin 1 Genetic disease PROTEIN Action Potentials Muscle Proteins 030204 cardiovascular system & hematology Rats Sprague-Dawley Mice 0302 clinical medicine BIO/09 - FISIOLOGIA EXOME DATA Heart Rate Caveolin Medicine and Health Sciences Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels Myocyte Myocytes Cardiac Mice Knockout Models Cardiovascular LOCALIZATION 3T3 Cells Electrophysiology Ion channels cardiovascular system Ion Channels and Arrhythmias Ion channel Cardiology and Cardiovascular Medicine Ion Channel Gating Arrhythmia Genetic diseases LONG-QT SYNDROME Biology MYOCYTES Caveolae Transfection LATE SODIUM CURRENT Kv1.5 Potassium Channel 03 medical and health sciences Physiology (medical) INFANT-DEATH-SYNDROME Animals Humans HCN4 Computer Simulation Transcription factor MUTATIONS Cardiac arrhythmia Arrhythmias Cardiac MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE Original Articles Fibroblasts Myocardial Contraction CHRONIC ATRIAL-FIBRILLATION Kinetics 030104 developmental biology Membrane protein Mutation Neuroscience |
| Zdroj: | Cardiovascular Research CARDIOVASCULAR RESEARCH |
| ISSN: | 1755-3245 0008-6363 |
| DOI: | 10.1093/cvr/cvx122 |
| Popis: | The identification of new molecular insights always drove the research. Data from genetic, molecular biology and biochemistry suggest new directions, open new fields and lead to new discoveries. The significance of these data is, in certain situation, difficult to envision. In this view, physiology could represent one of the possible read-out of the overall complex modifications inside the cell. In particular, electrophysiological analysis shed light on both physiological and pathological conditions in excitable and non-excitable cells. In excitable cell, ion channels, cellular microenvironment, transcription factors and accessory proteins shape the electric profile of the cell. In my PhD, I mainly used this approach to test the effect of mutations associated with arrhythmic diseases (in both cardiac arrhythmia and epilepsy) and of physiopathological remodeling in response to endurance training. In particular, I performed the following projects concerning: - Characterization of the biophysical properties of the hHCN1 L157V mutation found in a patient affected by idiopathic generalized epilepsy. This mutation resulted to decrease the current density and leading to an increased excitability in single neonatal rat cortical neurons. - Analysis of the cardiac endurance training-associated microRNAs (miRNAs) in a trained mouse model and of the role of the muscle-specific miRNAs in modulating membrane excitability in the neonatal rat ventricular cardiomyocytes. These results highlights new miRNAs potentially involved in the cardiac electrical remodeling associated with endurance training. - Characterization of the impact of the T78M cav-3 variant found in a cohort of arrhythmic patients. This variant induces modification of several ionic currents leading to a pro-arrhythmogenic profile. The leitmotiv of these projects is the identification of the causes underlying the pathophysiological modification of excitable cells by ion channels, membrane proteins and post-transcriptional molecules. |
| Databáze: | OpenAIRE |
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