Ultrastructural and functional alterations of EC coupling elements in mdx cardiomyocytes: an analysis from membrane surface to depth

Autor: Jean-François Faivre, Charlotte Lorin, Patrick Bois, Christian Cognard, Mélanie Gueffier, Stéphane Sebille
Přispěvatelé: Institut de Physiologie et Biologie Cellulaires (IPBC), Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Male
mdx mouse
Duchenne muscular dystrophy
[SDV]Life Sciences [q-bio]
Intracellular Space
MESH: Myocytes
Cardiac
Biochemistry
Mice
0302 clinical medicine
Sarcolemma
Myocyte
Myocytes
Cardiac
MESH: Animals
MESH: Sarcolemma
Excitation Contraction Coupling
0303 health sciences
biology
Ryanodine receptor
MESH: Mice
Inbred mdx
Depolarization
General Medicine
Anatomy
Molecular Imaging
medicine.anatomical_structure
MESH: Calcium
MESH: Intracellular Space
Dystrophin
Cardiomyopathy
Dilated
Biophysics
chemistry.chemical_element
Calcium
03 medical and health sciences
MESH: Excitation Contraction Coupling
medicine
Animals
MESH: Cardiomyopathy
Dilated
MESH: Mice
030304 developmental biology
MESH: Molecular Imaging
Cell Membrane
Skeletal muscle
Cell Biology
medicine.disease
MESH: Male
chemistry
biology.protein
Mice
Inbred mdx
030217 neurology & neurosurgery
MESH: Cell Membrane
Zdroj: Cell Biochemistry and Biophysics
Cell Biochemistry and Biophysics, Humana Press, 2013, 66 (3), pp.723-36. ⟨10.1007/s12013-013-9517-8⟩
ISSN: 1085-9195
DOI: 10.1007/s12013-013-9517-8⟩
Popis: International audience; A dilated cardiomyopathy (DCM) is associated with Duchenne muscular dystrophy (DMD). The loss of dystrophin leads to membrane instability and calcium dysregulation in skeletal muscle but effects of such a loss are not elucidated at cardiomyocytes level. We sought to examine whether membrane and transverse tubules damages occur in ventricular myocytes from mdx mouse model of DMD and how they impact the function of single excitation-contraction coupling elements. Scanning ion conductance microscopy (SICM) was used to characterize the integrity loss of living mdx cardiomyocytes surface. 2D Fourier transform analysis of labeled internal networks (transverse tubules, alpha-actinin, dihydropyridine receptors, ryanodine receptors) was performed to evaluate internal alterations. During calcium measurements, "smart microperfusions" of depolarizing solutions were applied through SICM nanopipette, stimulating single tubules elements. These approaches revealed structural membrane surface (39% decrease for Z-groove ratio) and transverse tubules disorganization (21% transverse tubules ratio decrease) in mdx as compared to control. These disruptions were associated with functional alterations (sixfold increase of calcium signal duration and twofold increase of sparks frequency). In DCM associated with DMD, myocytes display evident membrane alterations at the surface level but also in the cell depth with a disruption of transverse tubules network as observed in other cases of heart failure. These ultrastructural changes are associated with changes in the function of some coupling elements. Thus, these profound disruptions may play a role in calcium dysregulation through excitation-contraction coupling elements perturbation and suggest a transverse tubules stabilizing role for dystrophin.
Databáze: OpenAIRE
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