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RyR1-specific requirement for depolarization-induced Ca2+ sparks in urinary bladder smooth muscle
- 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.
- Subjects :
- medicine.medical_specialty
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
Myocytes, Smooth Muscle
Urinary Bladder
Mice, Transgenic
Tacrolimus Binding Protein 1A
Biology
Ryanodine receptor 2
Membrane Potentials
Mice
03 medical and health sciences
0302 clinical medicine
Caffeine
Internal medicine
medicine
Animals
Myocyte
Calcium Signaling
Cells, Cultured
ComputingMilieux_MISCELLANEOUS
030304 developmental biology
Mice, Knockout
Sirolimus
RYR1
0303 health sciences
Antibiotics, Antineoplastic
Ryanodine receptor
Endoplasmic reticulum
Skeletal muscle
Muscle, Smooth
Ryanodine Receptor Calcium Release Channel
Depolarization
Cell Biology
musculoskeletal system
Mice, Inbred C57BL
Endocrinology
medicine.anatomical_structure
FKBP
cardiovascular system
Calcium
Central Nervous System Stimulants
tissues
030217 neurology & neurosurgery
Subjects
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