Decreased expression of ryanodine receptors alters calcium-induced calcium release mechanism in mdx duodenal myocytes
J. Biol. Chem.. 2004-02-25; 279(20): 21287-21293
DOI: 10.1074/jbc.M311124200
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1. J Biol Chem. 2004 May 14;279(20):21287-93. Epub 2004 Feb 25.
Decreased expression of ryanodine receptors alters calcium-induced calcium
release mechanism in mdx duodenal myocytes.
Morel JL(1), Rakotoarisoa L, Jeyakumar LH, Fleischer S, Mironneau C, Mironneau J.
Author information:
(1)Laboratoire de Signalisation et Interactions Cellulaires, CNRS UMR 5017,
Université de Bordeaux II, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France.
It is generally believed that alterations of calcium homeostasis play a key role
in skeletal muscle atrophy and degeneration observed in Duchenne’s muscular
dystrophy and mdx mice. Mechanical activity is also impaired in gastrointestinal
muscles, but the cellular and molecular mechanisms of this pathological state
have not yet been investigated. We showed, in mdx duodenal myocytes, that both
caffeine- and depolarization-induced calcium responses were inhibited, whereas
acetylcholine- and thapsigargin-induced calcium responses were not significantly
affected compared with control mice. Calcium-induced calcium release efficiency
was impaired in mdx duodenal myocytes depending only on inhibition of ryanodine
receptor expression. Duodenal myocytes expressed both type 2 and type 3 ryanodine
receptors and were unable to produce calcium sparks. In control and mdx duodenal
myocytes, both caffeine- and depolarization-induced calcium responses were
dose-dependently and specifically inhibited with the anti-type 2 ryanodine
receptor antibody. A strong inhibition of type 2 ryanodine receptor in mdx
duodenal myocytes was observed on the mRNA as well as on the protein level. Taken
together, our results suggest that inhibition of type 2 ryanodine receptor
expression in mdx duodenal myocytes may account for the decreased calcium release
from the sarcoplasmic reticulum and reduced mechanical activity.
DOI: 10.1074/jbc.M311124200
PMID: 14985349 [Indexed for MEDLINE]