Abnormal membrane properties of the sarcoplasmic reticulum of pigs susceptible to malignant hyperthermia: modes of action of halothane, caffeine, dantrolene, and two other drugs.
Abnormal membrane properties of the sarcoplasmic reticulum of pigs susceptible to malignant hyperthermia: modes of action of halothane, caffeine, dantrolene, and two other drugs.
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易患恶性高热的猪肌浆网膜特性异常：氟烷、咖啡因、丹曲林和其他两种药物的作用方式。
DOI：
10.1016/0003-9861(86)90587-4
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发表时间：
1986
影响因子：
3.9
通讯作者：
Ohnishi,T
中科院分区：
文献类型：
--
作者：
Ohnishi,ST;Waring,AJ;Fang,SR;Horiuchi,K;Flick,JL;Sadanaga,KK;Ohnishi,T
用正常猪和遗传性高热易感猪的半腱肌重微粒体研究了肌浆网（SR）在恶性高热（MH）中的作用。在ATP存在下，SR负载有70 nmol Ca 2 +/mg SR蛋白。在这些条件下，MH-SR表现出Ca 2+诱导的Ca 2+释放（Ca-ICaR）和氟烷诱导的Ca 2+释放（氟烷-ICaR;氟烷浓度低至10 μm）。正常SR没有表现出这些释放现象。丹曲林抑制氟烷-ICaR，但不抑制Ca-ICaR。钌红和丁卡因抑制这两种类型的钙释放。从被动的Ca 2+流出的测量，结果表明，丹曲林不影响SR本身的Ca 2+渗透性，但只抑制氟烷诱导的渗透性增加。SR的膜序参数，测量的自旋探针EPR技术，表明氟烷紊乱的脂质双层的MH-SR在更大程度上比它没有正常SR。这种氟烷紊乱MH-SR的效果被拮抗丹曲林。钌红和丁卡因不拮抗氟烷的紊乱作用。这些结果提出了氟烷可能以这种方式干扰MH-SR中脂蛋白复合物的结构，从而打开Ca ~（2+）释放通道。由此释放的Ca 2+以正反馈方式通过Ca-ICaR机制进一步打开通道，从而触发MH综合征。丹曲林改善MH综合征的疗效可能与抑制氟烷效应有关。
The role of sarcoplasmic reticulum (SR) in malignant hyperthermia (MH) was studied using the heavy microsomal fraction prepared from semitendinosus muscles of both normal and genetically MH-susceptible pigs. In the presence of ATP, SR was loaded with 70 nmol Ca2+/mg SR protein. Under these conditions, MH-SR demonstrated Ca2+-induced Ca2+release (Ca-ICaR) and halothane-induced Ca2+release (halothane-ICaR; halothane concentrations as low as 10 μm). Normal SR did not demonstrate these release phenomena. Dantrolene inhibited the halothane-ICaR, but did not inhibit the Ca-ICaR. Ruthenium red and tetracaine inhibited both types of Ca2+release. From the measurement of passive Ca2+efflux, it was shown that dantrolene did not affect the Ca2+permeability of the SR itself, but suppressed only the halothane-induced increment of the permeability. The membrane order parameter of the SR, as measured by the spin-probe EPR technique, indicated that halothane disordered the lipid bilayer of MH-SR to a greater extent than it did of normal SR. This halothane disordering effect on MH-SR was antagonized by dantrolene. Ruthenium red and tetracaine did not antagonize the halothane disordering effect. These results raise the possibility that halothane could disturb the structure of the lipoprotein complex in MH-SR in such a way that it could open the Ca2+-release channels. The Ca2+thus released further opens the channel through the Ca-ICaR mechanism in a positive feedback fashion, thus triggering the MH syndrome. The efficacy of dantrolene in ameliorating the MH syndrome might be related to the inhibition of this halothane effect.
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DOI：
--
发表时间：
1974
期刊：
影响因子：
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作者：
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通讯作者：
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DOI：
--
发表时间：
1982
期刊：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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影响因子：
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