RyR1-specific requirement for depolarization-induced Ca2+ sparks in urinary bladder smooth muscle

Nicolas Fritz, Jean Luc Morel, Loice H. Jeyakumar, Sidney Fleischer, Paul D. Allen, Jean Mironneau, Nathalie Macrez

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Ryanodine receptor subtype 1 (RyR1) has been primarily characterized in skeletal muscle but several studies have revealed its expression in smooth muscle. Here, we used Ryr1-null mice to investigate the role of this isoform in Ca2+ signaling in urinary bladder smooth muscle. We show that RyR1 is required for depolarization-induced Ca2+ sparks, whereas RyR2 and RyR3 are sufficient for spontaneous or caffeine-induced Ca2+ sparks. Immunostaining revealed specific subcellular localization of RyR1 in the superficial sarcoplasmic reticulum; by contrast, RyR2 and RyR3 are mainly expressed in the deep sarcoplasmic reticulum. Paradoxically, lack of depolarization-induced Ca2+ sparks in Ryr1-/ - myocytes was accompanied by an increased number of cells displaying spontaneous or depolarization-induced Ca2+ waves. Investigation of protein expression showed that FK506-binding protein (FKBP) 12 and FKBP12.6 (both of which are RyR-associated proteins) are downregulated in Ryr1-/- myocytes, whereas expression of RyR2 and RyR3 are unchanged. Moreover, treatment with rapamycin, which uncouples FKBPs from RyR, led to an increase of RyR-dependent Ca2+ signaling in wild-type urinary bladder myocytes but not in Ryr1-/- myocytes. In conclusion, although decreased amounts of FKBP increase Ca2+ signals in Ryr1-/- urinary bladder myocytes the depolarization-induced Ca2+ sparks are specifically lost, demonstrating that RyR1 is required for depolarization-induced Ca2+ sparks and suggesting that the intracellular localization of RyR1 fine-tunes Ca2+ signals in smooth muscle.

Original languageEnglish (US)
Pages (from-to)3784-3791
Number of pages8
JournalJournal of Cell Science
Volume120
Issue number21
DOIs
StatePublished - Nov 1 2007
Externally publishedYes

Keywords

  • Ca sparks
  • FK506-binding protein
  • Ryanodine receptors
  • Ryr1 mice
  • Smooth muscle

ASJC Scopus subject areas

  • Cell Biology

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    Fritz, N., Morel, J. L., Jeyakumar, L. H., Fleischer, S., Allen, P. D., Mironneau, J., & Macrez, N. (2007). RyR1-specific requirement for depolarization-induced Ca2+ sparks in urinary bladder smooth muscle. Journal of Cell Science, 120(21), 3784-3791. https://doi.org/10.1242/jcs.009415