title: Physiological and Pathophysiological Insights of Nav1.4 and Nav1.5 Comparison.
abstract: Mutations in Nav1.4 and Nav1.5 α-subunits have been associated with muscular and cardiac channelopathies, respectively. Despite intense research on the structure and function of these channels, a lot of information is still missing to delineate the various physiological and pathophysiological processes underlying their activity at the molecular level. Nav1.4 and Nav1.5 sequences are similar, suggesting structural and functional homologies between the two orthologous channels. This also suggests that any characteristics described for one channel subunit may shed light on the properties of the counterpart channel subunit. In this review article, after a brief clinical description of the muscular and cardiac channelopathies related to Nav1.4 and Nav1.5 mutations, respectively, we compare the knowledge accumulated in different aspects of the expression and function of Nav1.4 and Nav1.5 α-subunits: the regulation of the two encoding genes (SCN4A and SCN5A), the associated/regulatory proteins and at last, the functional effect of the same missense mutations detected in Nav1.4 and Nav1.5. First, it appears that more is known on Nav1.5 expression and accessory proteins. Because of the high homologies of Nav1.5 binding sites and equivalent Nav1.4 sites, Nav1.5-related results may guide future investigations on Nav1.4. Second, the analysis of the same missense mutations in Nav1.4 and Nav1.5 revealed intriguing similarities regarding their effects on membrane excitability and alteration in channel biophysics. We believe that such comparison may bring new cues to the physiopathology of cardiac and muscular diseases.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, UMR 1087, l'Institut du ThoraxNantes, France; Centre National de la Recherche Scientifique, UMR 6291Nantes, France; Université de NantesNantes, France.
authors.forename: Gildas
authors.initials: G
authors.lastname: Loussouarn
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U1127Paris, France; Sorbonne Universités, Université Pierre-et-Marie-Curie, UMR S1127Paris, France; Centre National de la Recherche Scientifique, UMR 7225Paris, France; Institut du Cerveau et de la Moelle Épinière, ICMParis, France; Assistance Publique - Hôpitaux de Paris (AP-HP), Centres de Référence des Canalopathies Musculaires et des Maladies Neuro-musculaires Paris-EstParis, France; Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital de la Pitié Salpêtrière, Service de Biochimie Métabolique, Unité de Cardiogénétique et MyogénétiqueParis, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Sternberg
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U1127Paris, France; Sorbonne Universités, Université Pierre-et-Marie-Curie, UMR S1127Paris, France; Centre National de la Recherche Scientifique, UMR 7225Paris, France; Institut du Cerveau et de la Moelle Épinière, ICMParis, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Nicole
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, UMR 1087, l'Institut du ThoraxNantes, France; Centre National de la Recherche Scientifique, UMR 6291Nantes, France; Université de NantesNantes, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Marionneau
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, UMR 1087, l'Institut du ThoraxNantes, France; Centre National de la Recherche Scientifique, UMR 6291Nantes, France; Université de NantesNantes, France.
authors.forename: Francoise
authors.initials: F
authors.lastname: Le Bouffant
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, UMR 1087, l'Institut du ThoraxNantes, France; Centre National de la Recherche Scientifique, UMR 6291Nantes, France; Université de NantesNantes, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Toumaniantz
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, UMR 1087, l'Institut du ThoraxNantes, France; Centre National de la Recherche Scientifique, UMR 6291Nantes, France; Université de NantesNantes, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Barc
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, UMR 1087, l'Institut du ThoraxNantes, France; Centre National de la Recherche Scientifique, UMR 6291Nantes, France; Université de NantesNantes, France.
authors.forename: Olfat A
authors.initials: OA
authors.lastname: Malak
authors.affiliation: Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital de la Pitié Salpêtrière, Service de Biochimie Métabolique, Unité de Cardiogénétique et Myogénétique Paris, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Fressart
authors.affiliation: Centre Hospitalier Universitaire de Nantes, Centre de Référence Maladies Neuromusculaires Nantes-AngersNantes, France; Atlantic Gene Therapies - Biotherapy Institute for Rare DiseasesNantes, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Péréon
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, UMR 1087, l'Institut du ThoraxNantes, France; Centre National de la Recherche Scientifique, UMR 6291Nantes, France; Université de NantesNantes, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Baró
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, UMR 1087, l'Institut du ThoraxNantes, France; Centre National de la Recherche Scientifique, UMR 6291Nantes, France; Université de NantesNantes, France; Centre Hospitalier Universitaire de Nantes, l'Institut du ThoraxNantes, France.
authors.forename: Flavien
authors.initials: F
authors.lastname: Charpentier
keywords: Nav1.4; Nav1.5; associated/regulatory proteins; missense mutations; physiopathology
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