The decrease of expression of ryanodine receptor sub-type 2 is reversed by gentamycin sulphate in vascular myocytes from mdx mice

Jean-Luc Morel, Fabrice Dabertrand, Nicolas Fritz, Morgana Henaff, Jean Mironneau, Nathalie Macrez
Journal of Cellular and Molecular Medicine. 2009-02-27; 13(9b): 3122-3130
DOI: 10.1111/j.1582-4934.2009.00718.x

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1. J Cell Mol Med. 2009 Sep;13(9B):3122-30. doi: 10.1111/j.1582-4934.2009.00718.x.
Epub 2009 Feb 11.

The decrease of expression of ryanodine receptor sub-type 2 is reversed by
gentamycin sulphate in vascular myocytes from mdx mice.

Morel JL(1), Dabertrand F, Fritz N, Henaff M, Mironneau J, Macrez N.

Author information:
(1)Université de Bordeaux, CNRS, Centre Neurosciences Intégratives et Cognitives,
Unité Mixte de Recherche, Talence Cedex, France.

The mdx mouse, a model of the human Duchenne muscular dystrophy, displays
impaired contractile function in skeletal, cardiac and smooth muscles. We
explored the possibility that ryanodine receptor (RYR) expression could be
altered in vascular muscle. The three RYR sub-types were expressed in portal vein
myocytes. As observed through mRNA and protein levels, RYR2 expression was
strongly decreased in mdx myocytes, whereas RYR3 and RYR1 expression were
unaltered. The use of antisense oligonucleotide directed against RYR sub-types
indicated that caffeine-induced Ca(2+) response and Ca(2+) spark frequency
depended on RYR2 and RYR1. In mdx mice, caffeine-induced Ca(2+) responses were
decreased in both amplitude and maximal rate of rise, and the frequency of Ca(2+)
sparks was also strongly decreased. The gentamycin treatment was able to increase
both the expression of RYR2 and the caffeine-induced Ca(2+) response to the same
level as that observed in wild-type mice. Taken together, these results confirm
that both RYR1 and RYR2 are required for vascular Ca(2+) signalling and indicate
that inhibition of RYR2 expression may account for the decreased Ca(2+) release
from the SR in mdx vascular myocytes. Finally, we suggest that gentamycin can
restore the Ca(2+) signalling in smooth muscle from mdx mice by increasing RYR2
and dystrophin expression. These results may help explain the reduced efficacy of
contraction in vascular myocytes of mdx mice and Duchenne muscular
dystrophy-afflicted patients. Gentamycin treatment could be a good therapeutic
tool to restore the vascular function.

DOI: 10.1111/j.1582-4934.2009.00718.x
PMCID: PMC4516471
PMID: 19298530 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus