Different interactions of cardiac and skeletal muscle ryanodine receptors with FK-506 binding protein isoforms
Different interactions of cardiac and skeletal muscle ryanodine receptors with FK-506 binding protein isoforms
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DOI：
10.1152/ajpcell.1997.272.5.c1726
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发表时间：
1997-05-01
影响因子：
5.5
通讯作者：
Fleischer, S
中科院分区：
文献类型：
--
作者：
Barg, S;Copello, JA;Fleischer, S
在本研究中，我们比较了结合蛋白FKBP12和FKBP12.6与来自心脏（RyR（2））和骨骼肌（RyR（1））的兰尼碱受体的解离和重建的功能结果。骨骼肌RyR（1）通道在去除内源性结合的FKBP 12后被激活，这与以前的报道一致。FKBP12和FKBP12.6都与FKBP缺失的RyR（1）重新结合，并通过改变配体敏感性恢复其静止通道行为，如平面脂质双层中的单通道记录和通道的宏观行为（ryanodine结合和净能量化Ca2+摄取）所研究的。相比之下，使用与RyR相同类型的检测方法，从心脏RyR中去除FKBP 12.6（2）不会调节通道的功能（1）。FKBP12或FKBP12.6对FKBP12.6耗尽的心脏RyR的通道活性没有影响（2），尽管FKBP12.6重新结合。我们的研究揭示了两种兰尼碱受体亚型之间的重要差异，就其与FKBP12和FKBP12.6的功能相互作用而言。
In the present study, we compare functional consequences of dissociation and reconstitution of binding proteins FKBP12 and FKBP12.6 with ryanodine receptors from cardiac (RyR(2)) and skeletal muscle (RyR(1)). The skeletal muscle RyR(1) channel became activated on removal of endogenously bound FKBP12, consistent with previous reports. Both FKBP12 and FKBP12.6 rebind to FKBP-depleted RyR(1) and restore its quiescent channel behavior by altering Ligand sensitivity, as studied by single-channel recordings in planar lipid bilayers, and macroscopic behavior of the channels (ryanodine binding and net energized Ca2+ uptake). By contrast, removal of FKBP12.6 from the cardiac RyR(2) did not modulate the function of the channel using the same types of assays as for RyR(1). FKBP12 or FKBP12.6 had no effect on channel activity of FKBP12.6-depleted cardiac RyR(2), although FKBP12.6 rebinds. Our studies reveal important differences between the two ryanodine receptor isoforms with respect to their functional interaction with FKBP12 and FKBP12.6.