Submitted on February 19, 2007
Accepted on June 15, 2007
Role of RYR3 splice variants in calcium signalling in mouse non-pregnant and pregnant myometrium
Fabrice Dabertrand1, Nicolas Fritz2, Jean Mironneau3, Nathalie Macrez1, and Jean-Luc MOREL1*
1 CNIC, UMR5228, Talence, France
2 Medical Biochemistry and Biophysics, Karolinska Institut, stockolm, Sweden
3 UMR 5017, Bordeaux, France
* To whom correspondence should be addressed. E-mail: jlucmorel.cnic{at}voila.fr.
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 co-expressed in HEK293. Mouse myometrium expresses only RYR3 subtype, but the role of RYR3 isoforms obtained by alternative splicing and their activation by cyclic ADP-ribose during pregnancy have never been investigated. Here, we show that both isoforms RYR3S and RYR3L are differentially expressed in non-pregnant and pregnant mouse myometrium. The use of antisense oligonucleotides directed against each isoform indicated that only RYR3L was activated by caffeine and cyclic ADP-ribose in non-pregnant myometrium. These RYR3L-mediated Ca2+ release were negatively regulated by RYR3S expression. At the end of pregnancy, relative expression of RYR3L versus RYR3S and its ability to respond to cyclic ADP-ribose were increased. Therefore, our results suggest that physiological regulation of RYR3 alternative splicing may play an essential role at the end of pregnancy.
