Rectification of skeletal muscle ryanodine receptor mediated by FK506 binding protein.
Rectification of skeletal muscle ryanodine receptor mediated by FK506 binding protein.
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FK506 结合蛋白介导的骨骼肌兰尼碱受体的校正。
DOI：
10.1016/s0006-3495(95)80109-8
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Zhao,J
中科院分区：
文献类型：
--
作者：
Ma,J;Bhat,MB;Zhao,J
免疫抑制药物的胞质受体FK506结合蛋白（FKBP12）与骨骼肌肌浆网（SR）膜上的ryanodine受体保持紧密联系。FKBP12与ryanodine受体之间的相互作用导致Ca释放通道的明显整改。内源性fkbp结合的Ca释放通道将电流从SR管腔单向传导至肌浆；在相反的方向上，通道以快速的动力学失活。正如通道电导状态的变化所揭示的那样，FKBP12的结合可能会改变ryanodine受体复合物内的亚基相互作用。FKBP12与ryanodine受体结合的开启率和关闭率都明显依赖于膜电位，这表明FKBP12的结合位点位于Ca释放通道的传导孔内或附近。Ca释放通道的整流可以防止Ca从SR膜快速释放过程中的逆流，可能是一种参与肌肉兴奋-收缩耦合过程的负反馈机制。
The cytosolic receptor for immunosuppressant drugs, FK506 binding protein (FKBP12), maintains a tight association with ryanodine receptors of sarcoplasmic reticulum (SR) membrane in skeletal muscle. The interaction between FKBP12 and ryanodine receptors resulted in distinct rectification of the Ca release channel. The endogenous FKBP-bound Ca release channel conducted current unidirectionally from SR lumen to myoplasm; in the opposite direction, the channel deactivated with fast kinetics. The binding of FKBP12 is likely to alter subunit interactions within the ryanodine receptor complex, as revealed by changes in conductance states of the channel. Both on- and off-rates of FKBP12 binding to the ryanodine receptor showed clear dependence on the membrane potential, suggesting that the binding sites of FKBP12 reside in or near the conduction pore of the Ca release channel. Rectification of the Ca release channel would prevent counter-current flow during the rapid release of Ca from SR membrane, and thus may serve as a negative feedback mechanism that participates in the process of muscle excitation-contraction coupling.