Rapamycin inhibits activation of ryanodine receptors from skeletal muscle by the fatty acyl CoA-acyl CoA binding protein complex

Rosella Fulceri, Roberta Giunti, Jens Knudsen, Rosanna Leuzzi, T. Kardon, Angelo Benedetti

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

We previously showed that the fatty acyl CoA ester palmitoyl CoA (PCoA) complexed with a molar excess of its cytosolic binding protein (ACBP) causes a discrete Ca2+ efflux or allows Ca2+ release by suboptimal caffeine concentrations, in the Ca2+-preloaded terminal cisternae fraction (TC) from rabbit skeletal muscle, by activating ryanodine receptor Ca2+ release channels (RyRC). We show here that both effects were abolished by pretreating TC with the FKBP12 ligand rapamycin (20 μM). Moreover, rapamycin reversed the Ca2+ release induced by combined treatment with 3 mM caffeine and the PCoA-ACBP complex. Rapamycin also reduced the Ca2+-releasing activity by PCoA alone. Under the above experimental conditions, rapamycin removed FKBP12 from the TC membranes, as revealed by Western blot analysis. We conclude that FKBP12 associated with RyRC in the TC membrane participates in the activation of the Ca2+ channel by fatty acyl CoA esters.

Original languageEnglish
Pages (from-to)409-412
Number of pages4
JournalBiochemical and Biophysical Research Communications
Volume264
Issue number2
DOIs
Publication statusPublished - Oct 22 1999

Fingerprint

Diazepam Binding Inhibitor
Acyl Coenzyme A
Ryanodine Receptor Calcium Release Channel
Tacrolimus Binding Protein 1A
Sirolimus
Palmitoyl Coenzyme A
Muscle
Skeletal Muscle
Chemical activation
Caffeine
Esters
Membranes
Carrier Proteins
Western Blotting
Rabbits
Ligands

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Rapamycin inhibits activation of ryanodine receptors from skeletal muscle by the fatty acyl CoA-acyl CoA binding protein complex. / Fulceri, Rosella; Giunti, Roberta; Knudsen, Jens; Leuzzi, Rosanna; Kardon, T.; Benedetti, Angelo.

In: Biochemical and Biophysical Research Communications, Vol. 264, No. 2, 22.10.1999, p. 409-412.

Research output: Contribution to journalArticle

Fulceri, Rosella ; Giunti, Roberta ; Knudsen, Jens ; Leuzzi, Rosanna ; Kardon, T. ; Benedetti, Angelo. / Rapamycin inhibits activation of ryanodine receptors from skeletal muscle by the fatty acyl CoA-acyl CoA binding protein complex. In: Biochemical and Biophysical Research Communications. 1999 ; Vol. 264, No. 2. pp. 409-412.
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