Anesthetics alter the physical and functional properties of the Ca-ATPase in cardiac sarcoplasmic reticulum.
Anesthetics alter the physical and functional properties of the Ca-ATPase in cardiac sarcoplasmic reticulum.
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麻醉剂改变心脏肌浆网中 Ca-ATP 酶的物理和功能特性。
DOI：
10.1016/s0006-3495(95)80269-9
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Thomas,DD
中科院分区：
文献类型：
--
作者：
Karon,BS;Geddis,LM;Kutchai,H;Thomas,DD
我们研究了局部麻醉药利多卡因和全身麻醉药氟烷对心肌肌浆网（SR）CA-ATP酶功能和寡聚状态的影响。通过时间分辨磷光各向异性（TPA）检测寡聚体的变化。利多卡因抑制和聚集的Ca-ATP酶在心脏SR。微摩尔钙或0.5 M氯化锂保护对利多卡因诱导的抑制，表明静电相互作用是必不可少的利多卡因抑制的Ca-ATP酶。受磷蛋白（PLB）抗体2D 12，模拟PLB磷酸化，对利多卡因抑制心肌SR中的Ca-ATP酶没有影响。心肌SR中的Ca-ATP酶的抑制和聚集发生在比抑制和聚集骨骼SR中的Ca-ATP酶所需的浓度更低的利多卡因浓度下，表明该酶的心脏亚型对利多卡因具有更高的亲和力。氟烷对心肌SR的Ca-ATP酶有抑制和聚集作用。在PLB抗体存在或PLB被磷酸化时，氟烷对Ca-ATP酶的抑制和聚集作用均更强，表明PLB对氟烷诱导的抑制和聚集有保护作用。氟烷对心脏SR的作用与氟烷在骨骼SR中观察到的作用相反，在骨骼SR中氟烷激活并解离Ca-ATP酶。这些结果强调了蛋白质-蛋白质相互作用对Ca-ATP酶调节和心脏SR的麻醉扰动的关键作用。
We have studied the effects of the local anesthetic lidocaine, and the general anesthetic halothane, on the function and oligomeric state of the CA-ATPase in cardiac sarcoplasmic reticulum (SR). Oligomeric changes were detected by time-resolved phosphorescence anisotropy (TPA). Lidocaine inhibited and aggregated the Ca-ATPase in cardiac SR. Micromolar calcium or 0.5 M lithium chloride protected against lidocaine-induced inhibition, indicating that electrostatic interactions are essential to lidocaine inhibition of the Ca-ATPase. The phospholamban (PLB) antibody 2D12, which mimics PLB phosphorylation, had no effect on lidocaine inhibition of the Ca-ATPase in cardiac SR. Inhibition and aggregation of the Ca-ATPase in cardiac SR occurred at lower concentrations of lidocaine than necessary to inhibit and aggregate the Ca-ATPase in skeletal SR, suggesting that the cardiac isoform of the enzyme has a higher affinity for lidocaine. Halothane inhibited and aggregated the Ca-ATPase in cardiac SR. Both inhibition and aggregation of the Ca-ATPase by halothane were much greater in the presence of PLB antibody or when PLB was phosphorylated, indicating a protective effect of PLB on halothane-induced inhibition and aggregation. The effects of halothane on cardiac SR are opposite from the effects of halothane observed in skeletal SR, where halothane activates and dissociates the Ca-ATPase. These results underscore the crucial role of protein-protein interactions on Ca-ATPase regulation and anesthetic perturbation of cardiac SR.