Muscular dystrophy and cardiac defects: the calcium lead

Muscular dystrophy and cardiac defects: the calcium lead

The majority of patients suffering from Myotonic Dystrophy Type I (DM1) exhibit cardiac conduction disturbance, reducing their life expectancy and causing sometimes sudden death. In their last study (Auxerre-Plantié et al., 2019), the team “Diversification of muscle and heart cells in normal and pathological conditions” used the fruitfly as a model system to reveal that this cardiac conduction defects are linked to gene expression alteration in cellular calcium regulation pathways, offering a new therapeutic lead for DM1 cardiac involvement.

 In order to identify new candidates responsible for conduction disturbance in DM1, the tauthors  used the fruit fly model to reproduce the misbalance between two RNA binding proteins, involved in the disease. Using TU-tagging method to harvest cardiac-specific RNA combined to RNA-seq, they identified deregulations of several genes controlling cellular calcium levels, including abnormally high levels of straightjacket/α2δ3, which encodes a regulatory subunit of a voltage-gated calcium channel. This elevated α2δ3 expression is conserved in ventricular muscles from DM1 patients with conduction defects, suggesting that reducing the level of this calcium channel subunit may be of therapeutic benefit for the prevention of cardiac conduction defects in patients suffering from DM1.

This study has been publisshed in eLIFE: Auxerre-Plantié et al., 2019

A. The adult Drosophila heart expressing Hand-Gal4-driven GFP (Hand>GFP). B. M-modes illustrating ‘partial’ and ‘total’ heart blocks observed in DM1 models (Hand>MblRNAi and Hand>Bru-3) flies developing conduction defects. C. A scheme illustrating normal and DM1 conditions with low and increased α2δ3 levels in ventricular muscle, respectively. In pathological context, the aberrant inward calcium current in ventricular cardiomyocytes could lead to conduction defects and in particular to the IVCD.

Last modified: 07/07/2020