Decreased expression of ryanodine receptors alters calcium-induced calcium release mechanism in mdx duodenal myocytes.
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.
Morel
Jean-Luc
JL
Laboratoire de Signalisation et Interactions Cellulaires, CNRS UMR 5017, Université de Bordeaux II, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France.
Rakotoarisoa
Lala
L
Jeyakumar
Loice H
LH
Fleischer
Sidney
S
Mironneau
Chantal
C
Mironneau
Jean
J
D000818:Animals; D002118:Calcium / Q000502:physiology*; D020013:Calcium Signaling; D004386:Duodenum / Q000503:physiopathology*; D005786:Gene Expression Regulation / Q000235:genetics*; D008564:Membrane Potentials; D051379:Mice; D008810:Mice, Inbred C57BL; D008861:Microsomes / Q000378:metabolism; D032342:Muscle Cells / Q000502:physiology*; D009130:Muscle, Smooth / Q000503:physiopathology; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000503:physiopathology*; D012433:Ryanodine / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*
D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine; D002118:Calcium