RyR1-specific requirement for depolarization-induced Ca2+ sparks in urinary bladder smooth muscle
Journal of Cell Science. 2007-10-09; 120(21): 3784-3791
DOI: 10.1242/jcs.009415
Lire sur PubMed
1. J Cell Sci. 2007 Nov 1;120(Pt 21):3784-91. Epub 2007 Oct 9.
RyR1-specific requirement for depolarization-induced Ca2+ sparks in urinary
bladder smooth muscle.
Fritz N(1), Morel JL, Jeyakumar LH, Fleischer S, Allen PD, Mironneau J, Macrez N.
Author information:
(1)CNRS UMR 5017, Laboratoire de Signalisation et Interactions Cellulaires,
Université Bordeaux 2, Bordeaux, France.
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 Ca(2+)
signaling in urinary bladder smooth muscle. We show that RyR1 is required for
depolarization-induced Ca(2+) sparks, whereas RyR2 and RyR3 are sufficient for
spontaneous or caffeine-induced Ca(2+) 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 Ca(2+) sparks in Ryr1(-/-) myocytes
was accompanied by an increased number of cells displaying spontaneous or
depolarization-induced Ca(2+) 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 Ca(2+)
signaling in wild-type urinary bladder myocytes but not in Ryr1(-/-) myocytes. In
conclusion, although decreased amounts of FKBP increase Ca(2+) signals in
Ryr1(-/-) urinary bladder myocytes the depolarization-induced Ca(2+) sparks are
specifically lost, demonstrating that RyR1 is required for depolarization-induced
Ca(2+) sparks and suggesting that the intracellular localization of RyR1
fine-tunes Ca(2+) signals in smooth muscle.
DOI: 10.1242/jcs.009415
PMID: 17925380 [Indexed for MEDLINE]