Requirement for the ryanodine receptor type 3 for efficient contraction in neonatal skeletal muscles
Requirement for the ryanodine receptor type 3 for efficient contraction in neonatal skeletal muscles
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DOI：
10.1093/emboj/16.23.6956
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发表时间：
1997-12-01
期刊：
影响因子：
11.4
通讯作者：
Sorrentino, V
中科院分区：
文献类型：
--
作者：
Bertocchini, F;Ovitt, CE;Sorrentino, V
钙释放通道的骨架亚型RyR1在激活骨骼肌收缩中起核心作用，最近在一些哺乳动物的骨骼肌中观察到另一种亚型RyR3，但它是否参与调节骨骼肌收缩尚不清楚。从胚胎晚期到成年，小鼠骨骼肌中RyR3的表达被研究，发现RyR3在出生后肌肉发育阶段广泛表达于小鼠骨骼肌，但在成年小鼠的肌肉中检测不到RyR3。除横隔肌和比目鱼肌外，RyR3基因敲除小鼠产生了RyR3基因敲除小鼠。结果表明，新生RyR3(-/-)小鼠的骨骼肌收缩在出生后的第一周就受到了损害，电刺激引起的抽动和咖啡因引起的收缩都受到了强烈的抑制，这些结果首次证明了RyR3在新生骨骼肌的兴奋-收缩偶联中具有生理作用，RyR3的低含量与RyR3基因敲除的巨大影响之间的不比例表明，这种异构体有助于兰诺定受体(RyR1)现有群体释放的钙离子的放大。
The skeletal isoform of Ca2+ release channel, RyR1, plays a central role in activation of skeletal muscle contraction, Another isoform, RyR3, has been observed recently in some mammalian skeletal muscles, but whether it participates in regulating skeletal muscle contraction is not known, The expression of RyR3 in skeletal muscles was studied in mice from late fetal stages to adult life, RyR3 was found to be expressed widely in murine skeletal muscles during the post-natal phase of muscle development, but was not detectable in muscles of adult mice, with the exception of the diaphragm and soleus muscles, RyR3 knockout mice were generated, and it was shown that skeletal muscle contraction in these mice was impaired during the first weeks after birth, In skeletal muscles isolated from newborn RyR3(-/-) mice, hut not in those from adult mice, the twitch elicited by electrical stimulation and the contracture induced by caffeine were strongly depressed, These results provide the first evidence that RyR3 has a physiological role in excitation-contraction coupling of neonatal skeletal muscles, The disproportion between the low amount of RyR3 and the large impact of the RyR3 knockout suggests that this isoform contributes to the amplification of Ca2+ released by the existing population of ryanodine receptors (RyR1).