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

Authors :
Nathalie Macrez
Sidney Fleischer
Nicolas Fritz
Jean Mironneau
Paul D. Allen
Jean-Luc Morel
Loice H. Jeyakumar
Météo-France [Paris]
Météo France
Signalisation et interactions cellulaires (SIC)
Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS)
St. Vincent's Hospital, Sydney
Laboratoire de Physiologie Cellulaire et Pharmacologie Moléculaire, INSERM CJF 88-13, Université de Bordeaux II, France.
Institut des Maladies Neurodégénératives [Bordeaux] (IMN)
Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)
Source :
Journal of Cell Science, Journal of Cell Science, Company of Biologists, 2007, 120 (21), pp.3784-3791. ⟨10.1242/jcs.009415⟩
Publication Year :
2007
Publisher :
HAL CCSD, 2007.

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.

Details

Language :
English
ISSN :
00219533 and 14779137
Database :
OpenAIRE
Journal :
Journal of Cell Science, Journal of Cell Science, Company of Biologists, 2007, 120 (21), pp.3784-3791. ⟨10.1242/jcs.009415⟩
Accession number :
edsair.doi.dedup.....7d8151125248fc43c598334962598180