title: Axial stretch-dependent cation entry in dystrophic cardiomyopathy: Involvement of several TRPs channels.
abstract: In Duchenne muscular dystrophy (DMD), deficiency of the cytoskeletal protein dystrophin leads to well-described defects in skeletal muscle but also to dilated cardiomyopathy (DCM). In cardiac cells, the subsarcolemmal localization of dystrophin is thought to protect the membrane from mechanical stress. The dystrophin deficiency leads to membrane instability and a high stress-induced Ca(2+) influx due to dysregulation of sarcolemmal channels such as stretch-activated channels (SACs). In this work divalent cation entry has been explored in isolated ventricular Wild Type (WT) and mdx cardiomyocytes in two different conditions: at rest and during the application of an axial stretch. At rest, our results suggest that activation of TRPV2 channels participates to a constitutive basal cation entry in mdx cardiomyocytes.Using microcarbon fibres technique, an axial stretchwas applied to mimic effects of physiological conditions of ventricular filling and study on cation influx bythe Mn(2+)-quenching techniquedemonstrated a high stretch-dependentcationic influx in dystrophic cells, partially due to SACs. Involvement of TRPs channels in this excessive Ca(2+) influx has been investigated using specific modulators and demonstratedboth sarcolemmal localization and an abnormal activity of TRPV2 channels. In conclusion, TRPV2 channels are demonstrated here to play a key role in cation influx and dysregulation in dystrophin deficient cardiomyocytes, enhanced in stretching conditions.
authors.affiliation: Laboratoire de Signalisation et Transports Ioniques Membranaires (STIM CNRS ERL 7368), Equipe Transferts Ioniques et Rythmicité Cardiaque (TIRC), Université de Poitiers, 86073 Poitiers Cedex 9, France.
authors.forename: E
authors.initials: E
authors.lastname: Aguettaz
authors.affiliation: Laboratoire de Signalisation et Transports Ioniques Membranaires (STIM CNRS ERL 7368), Equipe Calcium et Microenvironnement des Cellules Souches (CMCS), Université de Poitiers, 86073 Poitiers Cedex 9, France.
authors.forename: J J
authors.initials: JJ
authors.lastname: Lopez
authors.affiliation: Laboratoire de Signalisation et Transports Ioniques Membranaires (STIM CNRS ERL 7368), Equipe Transferts Ioniques et Rythmicité Cardiaque (TIRC), Université de Poitiers, 86073 Poitiers Cedex 9, France.
authors.forename: A
authors.initials: A
authors.lastname: Krzesiak
authors.affiliation: INSERM U955 and Département de Physiologie, Hôpital Henri Mondor, AP-HP, Université Paris-Est Créteil (UPEC), 94010 Créteil, France.|Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: L
authors.initials: L
authors.lastname: Lipskaia
authors.affiliation: INSERM U955 and Département de Physiologie, Hôpital Henri Mondor, AP-HP, Université Paris-Est Créteil (UPEC), 94010 Créteil, France.
authors.forename: S
authors.initials: S
authors.lastname: Adnot
authors.affiliation: Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Hajjar
authors.affiliation: Laboratoire de Signalisation et Transports Ioniques Membranaires (STIM CNRS ERL 7368), Equipe Transferts Ioniques et Rythmicité Cardiaque (TIRC), Université de Poitiers, 86073 Poitiers Cedex 9, France.
authors.forename: C
authors.initials: C
authors.lastname: Cognard
authors.affiliation: Laboratoire de Signalisation et Transports Ioniques Membranaires (STIM CNRS ERL 7368), Equipe Calcium et Microenvironnement des Cellules Souches (CMCS), Université de Poitiers, 86073 Poitiers Cedex 9, France.
authors.forename: B
authors.initials: B
authors.lastname: Constantin
authors.affiliation: Laboratoire de Signalisation et Transports Ioniques Membranaires (STIM CNRS ERL 7368), Equipe Transferts Ioniques et Rythmicité Cardiaque (TIRC), Université de Poitiers, 86073 Poitiers Cedex 9, France.
authors.forename: S
authors.initials: S
authors.lastname: Sebille
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D009202:Cardiomyopathies / Q000378:metabolism*; D016189:Dystrophin / Q000378:metabolism; D008810:Mice, Inbred C57BL; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D016189:Dystrophin; D050916:TRPV Cation Channels; C485717:Trpv2 protein, mouse; D002118:Calcium
keywords: Calcium; Dilated cardiomyopathy; Duchenne muscular dystrophy; Mdx; Mechanosensitivity; Membrane stretch; Stretch-activated channels; TRPCs; TRPV2