Flucher B E, Conti A, Takeshima H, Sorrentino V
Department of Physiology, University of Innsbruck, A-6020 Innsbruck, Austria.
J Cell Biol. 1999 Aug 9;146(3):621-30. doi: 10.1083/jcb.146.3.621.
The type 3 ryanodine receptor (RyR3) is a ubiquitous calcium release channel that has recently been found in mammalian skeletal muscles. However, in contrast to the skeletal muscle isoform (RyR1), neither the subcellular distribution nor the physiological role of RyR3 are known. Here, we used isoform-specific antibodies to localize RyR3 in muscles of normal and RyR knockout mice. In normal hind limb and diaphragm muscles of young mice, RyR3 was expressed in all fibers where it was codistributed with RyR1 and with the skeletal muscle dihydropyridine receptor. This distribution pattern indicates that RyR3 is localized in the triadic junctions between the transverse tubules and the sarcoplasmic reticulum. During development, RyR3 expression declined rapidly in some fibers whereas other fibers maintained expression of RyR3 into adulthood. Comparing the distribution of RyR3-containing fibers with that of known fiber types did not show a direct correlation. Targeted deletion of the RyR1 or RyR3 gene resulted in the expected loss of the targeted isoform, but had no adverse effects on the expression and localization of the respective other RyR isoform. The localization of RyR3 in skeletal muscle triads, together with RyR1, is consistent with an accessory function of RyR3 in skeletal muscle excitation-contraction coupling.
3型兰尼碱受体（RyR3）是一种普遍存在的钙释放通道，最近在哺乳动物骨骼肌中被发现。然而，与骨骼肌亚型（RyR1）不同，RyR3的亚细胞分布和生理作用均不为人所知。在此，我们使用亚型特异性抗体将RyR3定位在正常小鼠和RyR基因敲除小鼠的肌肉中。在幼鼠的正常后肢和膈肌中，RyR3在所有纤维中均有表达，且与RyR1和骨骼肌二氢吡啶受体共分布。这种分布模式表明RyR3定位于横小管和肌浆网之间的三联体连接处。在发育过程中，RyR3在一些纤维中的表达迅速下降，而其他纤维则维持RyR3的表达直至成年。将含有RyR3的纤维分布与已知纤维类型的分布进行比较，未发现直接相关性。靶向敲除RyR1或RyR3基因导致预期的靶向亚型缺失，但对另一种RyR亚型的表达和定位没有不利影响。RyR3与RyR1一起定位于骨骼肌三联体中，这与RyR3在骨骼肌兴奋-收缩偶联中的辅助功能一致。
