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Altered microtubule structure, hemichannel localization and beating activity in cardiomyocytes expressing pathologic nuclear lamin A/C
- Source :
- Heliyon, vol 6, iss 1, Heliyon, Vol 6, Iss 1, Pp e03175-(2020), Heliyon
- Publication Year :
- 2020
- Publisher :
- eScholarship, University of California, 2020.
-
Abstract
- Given the clinical effect of laminopathies, understanding lamin mechanical properties will benefit the treatment of heart failure. Here we report a mechano-dynamic study of LMNA mutations in neonatal rat ventricular myocytes (NRVM) using single cell spectroscopy with Atomic Force Microscopy (AFM) and measured changes in beating force, frequency and contractile amplitude of selected mutant-expressing cells within cell clusters. Furthermore, since beat-to-beat variations can provide clues on the origin of arrhythmias, we analyzed the beating rate variability using a time-domain method which provides a Poincaré plot. Data were further correlated to cell phenotypes. Immunofluorescence and calcium imaging analysis showed that mutant lamin changed NRVMs beating force and frequency. Additionally, we noted an altered microtubule network organization with shorter filament length, and defective hemichannel membrane localization (Connexin 43). These data highlight the interconnection between nucleoskeleton, cytoskeleton and sarcolemmal structures, and the transcellular consequences of mutant lamin protein in the pathogenesis of the cardiac laminopathies.<br />Biological sciences; Cardiology; Biomechanics; Cytoskeleton; Mechanical property; Membrane; Lamin A/C; Cardiomyopathy; Atomic force microscopy; Cardiomyocytes; Beating; Cx43
- Subjects :
- 0301 basic medicine
Biological science
Cardiomyopathy
Cell
Biomechanic
Cardiology
Connexin
Bioengineering
Cardiomyocyte
Cardiovascular
Article
LMNA
03 medical and health sciences
Atomic force microscopy
0302 clinical medicine
Calcium imaging
Microtubule
medicine
2.1 Biological and endogenous factors
Biomechanics
lcsh:Social sciences (General)
Aetiology
Cytoskeleton
lcsh:Science (General)
Mechanical property
Cardiomyocytes
Lamin A/C
Multidisciplinary
Chemistry
Membrane
Biological sciences
Beating
Cx43
Cell biology
030104 developmental biology
medicine.anatomical_structure
Heart Disease
Nuclear lamina
lcsh:H1-99
030217 neurology & neurosurgery
Lamin
lcsh:Q1-390
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Heliyon, vol 6, iss 1, Heliyon, Vol 6, Iss 1, Pp e03175-(2020), Heliyon
- Accession number :
- edsair.doi.dedup.....6cec31159ae62f6eb78135bb9b902f64