| First Author | Matsuki K | Year | 2017 |
| Journal | Pflugers Arch | Volume | 469 |
| Issue | 2 | Pages | 313-326 |
| PubMed ID | 27866274 | Mgi Jnum | J:263241 |
| Mgi Id | MGI:6188998 | Doi | 10.1007/s00424-016-1900-z |
| Citation | Matsuki K, et al. (2017) Ryanodine receptor type 3 does not contribute to contractions in the mouse myometrium regardless of pregnancy. Pflugers Arch 469(2):313-326 |
| abstractText | Ryanodine receptor type 3 (RyR3) is expressed in myometrial smooth muscle cells (MSMCs). The short isoform of RyR3 is a dominant negative variant (DN-RyR3) and negatively regulates the functions of RyR2 and full-length (FL)-RyR3. DN-RyR3 has been suggested to function as a major RyR3 isoform in non-pregnant (NP) mouse MSMCs, and FL-RyR3 may also be upregulated during pregnancy (P). This increase in the FL-RyR3/DN-RyR3 ratio may contribute to the strong contractions by MSMCs for parturition. In the present study, spontaneous contractions by the myometrium in NP and P mice were highly susceptible to nifedipine but were not affected by ryanodine. Ca(2+) image analyses under a voltage clamp revealed that the influx of Ca(2+) through voltage-dependent Ca(2+) channels did not cause the release of Ca(2+) from the sarcoplasmic reticulum (SR). Cytosolic Ca(2+) concentrations ([Ca(2+)]cyt) in MSMCs were not affected by caffeine. Despite the abundant expression of large conductance Ca(2+)-activated K(+) channels in MSMCs, spontaneous transient outward currents were not observed in the resting state because of the substantive lack of Ca(2+) sparks. Quantitative PCR and Western blot analyses indicated that DN-RyR3 was strongly expressed in the NP myometrium, while the expression of FL-RyR3 and DN-RyR3 was markedly reduced in the P myometrium. The messenger RNA (mRNA) expression of RyR2 and RyR1 was negligible in the NP and P myometria. Moreover, RyR3 knockout mice may become pregnant and deliver normally. Thus, we concluded that none of the RyR subtypes, including RyR3, play a significant role in the regulation of [Ca(2+)]cyt in or contractions by mouse MSMCs regardless of pregnancy. |
