Role of RYR3 splice variants in calcium signaling in mouse nonpregnant and pregnant myometrium

Laboratoire de Signalisation et Interactions Cellulaires, Centre National de la Recherche Scientifique UMR5017, Université Bordeaux, Bordeaux, France Submitted 19 February 2007 ; accepted in final form 15 June 2007 Alternative splicing of ryanodine receptor subtype 3 (RYR3) may generate a short isof...

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Bibliographic Details
Published in:American Journal of Physiology: Cell Physiology 2007-09, Vol.293 (3), p.C848-C854
Main Authors: Dabertrand, Fabrice, Fritz, Nicolas, Mironneau, Jean, Macrez, Nathalie, Morel, Jean-Luc
Format: Article
Language:English
Subjects:
Alternative Splicing - physiology
Animals
Caffeine - pharmacology
Calcium
Calcium - metabolism
Calcium Signaling - drug effects
Calcium Signaling - physiology
Cyclic ADP-Ribose - metabolism
Female
Gene expression
Gene Expression Regulation - physiology
Life Sciences
Medicin och hälsovetenskap
Mice
Muscular system
Myocytes, Smooth Muscle - cytology
Myocytes, Smooth Muscle - metabolism
Myometrium - cytology
Neurobiology
Neurons and Cognition
Oligonucleotides, Antisense - pharmacology
Phosphodiesterase Inhibitors - pharmacology
Pregnancy
Pregnancy, Animal - physiology
Reproductive system
Rodents
Ryanodine Receptor Calcium Release Channel - genetics
Ryanodine Receptor Calcium Release Channel - metabolism
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Summary:Laboratoire de Signalisation et Interactions Cellulaires, Centre National de la Recherche Scientifique UMR5017, Université Bordeaux, Bordeaux, France Submitted 19 February 2007 ; accepted in final form 15 June 2007 Alternative splicing of ryanodine receptor subtype 3 (RYR3) may generate a short isoform (RYR3S) without channel function and a functional full-length isoform (RYR3L). The RYR3S isoform has been shown to negatively regulate the native RYR2 subtype in smooth muscle cells as well as the RYR3L isoform when both isoforms were coexpressed in HEK-293 cells. Mouse myometrium expresses only the RYR3 subtype, but the role of RYR3 isoforms obtained by alternative splicing and their activation by cADP-ribose during pregnancy have never been investigated. Here, we show that both RYR3S and RYR3L isoforms are differentially expressed in nonpregnant and pregnant mouse myometrium. The use of antisense oligonucleotides directed against each isoform indicated that only RYR3L was activated by caffeine and cADP-ribose in nonpregnant myometrium. These RYR3L-mediated Ca 2+ releases were negatively regulated by RYR3S expression. At the end of pregnancy, the relative expression of RYR3L versus RYR3S and its ability to respond to cADP-ribose were increased. Therefore, our results suggest that physiological regulation of RYR3 alternative splicing may play an essential role at the end of pregnancy. ryanodine receptor; smooth muscle; alternative splicing Address for reprint requests and other correspondence: J.-L. Morel, Centre de Neurosciences Intégratives et Cognitives, UMR5228 CNRS, Université Bordeaux 1 and Université Bordeaux 2, Ave. des Facultés, Talence 33405, France (e-mail: jlucmorel.cnic{at}voila.fr )
ISSN:0363-6143
1522-1563
DOI:10.1152/ajpcell.00069.2007