RyR1-specific requirement for depolarization-induced Ca2+ sparks in urinary bladder smooth muscle
Journal of Cell Science. 2007-10-09; 120(21): 3784-3791
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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.
(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.
PMID: 17925380 [Indexed for MEDLINE]