IRIS – Institutional Research Information System
IRIS è il sistema di gestione della ricerca dell’Università degli Studi di Milano-Bicocca.Il repository BOA è il modulo del sistema dedicato alla raccolta e alla disseminazione della produzione scientifica di Ateneo. Le pubblicazioni sono ricercabili per parola chiave attraverso il box nella barra orizzontale in alto oppure, mediante il pulsante Sfoglia, per "Afferenza", "Autore", "Titolo", "Tipologia" o "Settore scientifico-disciplinare".
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EnglishBACKGROUND: Calmodulin (CaM) mutations have been identified recently in subjects with congenital long QT syndrome (LQTS) or catecholaminergic polymorphic ventricular tachycardia (CPVT), but the mechanisms responsible for these divergent arrhythmia-susceptibility syndromes in this context are unknown. We tested the hypothesis that LQTS-associated CaM mutants disrupt Ca2+ homeostasis in developing cardiomyocytes possibly by affecting either late Na current or Ca2+-dependent inactivation of L-type Ca2+ current. METHODS AND RESULTS: We coexpressed CaM mutants with the human cardiac Na channel (NaV1.5) in tsA201 cells, and we used mammalian fetal ventricular cardiomyocytes to investigate LQTS- and CPVT-associated CaM mutations (LQTS- and CPVT-CaM). LQTS-CaM mutants do not consistently affect L-type Na current in heterologous cells or native cardiomyocytes, suggesting that the Na channel does not contribute to LQTS pathogenesis in the context of CaM mutations. LQTS-CaM mutants (D96V, D130G, F142L) impaired Ca2+-dependent inactivation, whereas the CPVT-CaM mutant N54I had no effect on Ca2+-dependent inactivation. LQTS-CaM mutants led to loss of Ca2+-transient entrainment with the rank order from greatest to least effect: CaM-D130G~CaM-D96V>>CaM-F142L. This rank order follows measured Ca2+-CaM affinities for wild-type and mutant CaM. Acute isoproterenol restored entrainment for CaM-130G and CaM-D96V but caused irreversible cytosolic Ca2+ overload for cells expressing a CPVT-CaM mutant. CONCLUSIONS: CaM mutations associated with LQTS may not affect L-type Na+ current but may evoke defective Ca2+-dependent inactivation of L-type Ca2+ current
Yin, G., Hassan, F., Haroun, A., Murphy, L., Crotti, L., Schwartz, P., et al. (2014). Arrhythmogenic calmodulin mutations disrupt intracellular cardiomyocyte Ca2+ regulation by distinct mechanisms. JOURNAL OF THE AMERICAN HEART ASSOCIATION. CARDIOVASCULAR AND CEREBROVASCULAR DISEASE, 3(3), 1-14 [10.1161/JAHA.114.000996].
| Citazione: | Yin, G., Hassan, F., Haroun, A., Murphy, L., Crotti, L., Schwartz, P., et al. (2014). Arrhythmogenic calmodulin mutations disrupt intracellular cardiomyocyte Ca2+ regulation by distinct mechanisms. JOURNAL OF THE AMERICAN HEART ASSOCIATION. CARDIOVASCULAR AND CEREBROVASCULAR DISEASE, 3(3), 1-14 [10.1161/JAHA.114.000996]. | |
| Tipo: | Articolo in rivista - Articolo scientifico | |
| Carattere della pubblicazione: | Scientifica | |
| Presenza di un coautore afferente ad Istituzioni straniere: | Si | |
| Titolo: | Arrhythmogenic calmodulin mutations disrupt intracellular cardiomyocyte Ca2+ regulation by distinct mechanisms | |
| Autori: | Yin, G; Hassan, F; Haroun, A; Murphy, L; Crotti, L; Schwartz, P; George, A; Satin, J | |
| Autori: | ||
| Data di pubblicazione: | 2014 | |
| Lingua: | English | |
| Rivista: | JOURNAL OF THE AMERICAN HEART ASSOCIATION. CARDIOVASCULAR AND CEREBROVASCULAR DISEASE | |
| Digital Object Identifier (DOI): | http://dx.doi.org/10.1161/JAHA.114.000996 | |
| Appare nelle tipologie: | 01 - Articolo su rivista |
File in questo prodotto:
| File | Descrizione | Tipologia | Licenza | |
|---|---|---|---|---|
| Yin 2014 J Am Heart Assoc.pdf | N/A | Open Access Visualizza/Apri |
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