Altered binding site for Ca2+ in the ryanodine receptor of human malignant hyperthermia.
Altered binding site for Ca2+ in the ryanodine receptor of human malignant hyperthermia.
复制标题
人类恶性高热的兰尼碱受体中 Ca2 的结合位点发生改变。
DOI：
10.1152/ajpcell.1991.261.2.c237
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Coronado,R
中科院分区：
文献类型：
--
作者：
Valdivia,HH;Hogan,K;Coronado,R
[3H]ryanodine是一种形成肌浆网Ca2+释放通道的受体复合物的特异性配体，研究了[3H]ryanodine在正常(N)和恶性高热易感（MH）人类骨骼肌中的结合特性。通过平面双分子层的单通道记录以及Ca2+释放通道的激活剂和抑制剂对[3H]良嘌呤结合特性产生的变化，证明了溶解的良嘌呤受体的完整性。N和MH受体能够以Ca（2+）依赖的方式结合[3H]ryanodine。Scatchard分析表明，在N肌和MH肌中均存在[3H]ryanodine的单一结合位点。当Ca2+浓度大于30微米时，N和MH的结合亲和力基本相同（Kd约为7 nM）。在0.3 microM Ca2+下，MH受体对[3H]ryanodine的亲和力（Kd = 4.1 +/- 1.0 nM）高于N受体（Kd = 7.1 +/- 0.8 nM）。MH肌中[3H]ryanodine的单个Kd的存在，与N肌不同，表明MH肌没有可检测到的N受体水平。[3H]ryanodine对Ca2+的依赖性进一步表明，MH受体对Ca2+的亲和力（Kd[Ca2+] = 120 +/- 50 nM）高于N受体（Kd[Ca2+] = 250 +/- 80 nM）。咖啡因增加了[3H]ryanodine在亚微摩尔[Ca2+]上的结合，对MH的影响更大。咖啡因对N和MH受体的表观亲和力常数分别为13 +/- 1.8 mM和6 +/- 0.8 mM。显然，mh易感人体骨骼肌的ryanodine受体对Ca2+具有异常高的敏感性，咖啡因增强了这种敏感性。（摘要删节250字）
The binding properties of [3H]ryanodine, a specific ligand of the receptor complex that forms the Ca2+ release channel of sarcoplasmic reticulum, were studied in normal (N) and malignant hyperthermia-susceptible (MH) human skeletal muscle. Integrity of the solubilized ryanodine receptor was demonstrated by single-channel recordings in planar bilayers and by the changes produced by activators and inhibitors of the Ca2+ release channel on the binding properties of [3H]ryanodine. N and MH receptors were capable of binding [3H]ryanodine in a Ca(2+)-dependent manner. Scatchard analysis showed that a single binding site for [3H]ryanodine was present in either N or MH muscle. Binding affinity was approximately the same in N and MH (Kd approximately 7 nM), when the Ca2+ concentration was greater than 30 microM. At 0.3 microM Ca2+, MH receptors displayed a higher affinity for [3H]ryanodine (Kd = 4.1 +/- 1.0 nM) than N receptors (Kd = 7.1 +/- 0.8 nM). The presence of a single Kd for [3H]ryanodine in MH muscle, distinct from that of N muscle, indicated that MH muscle does not have detectable levels of N receptors. Ca2+ dependence of [3H]ryanodine binding further suggested that MH receptors had a higher affinity for Ca2+ (Kd[Ca2+] = 120 +/- 50 nM) than N receptors (Kd[Ca2+] = 250 +/- 80 nM). Caffeine increased [3H]ryanodine binding at submicromolar [Ca2+], and the effect was larger in MH. Apparent affinity constants for caffeine were 13 +/- 1.8 mM in N and 6 +/- 0.8 mM in MH receptors. Evidently, the ryanodine receptor of MH-susceptible human skeletal muscle has an unusually high sensitivity to Ca2+ which is augmented by caffeine.(ABSTRACT TRUNCATED AT 250 WORDS)
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影响因子：
5.7
作者：
M. G. Larach
通讯作者：
M. G. Larach
DOI：
10.1016/s0021-9258(18)61565-0
发表时间：
1987-02
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
F. Lattanzio;Robert;Schlattererl;Michael Nicart;Kevin;Campbell;John L. SutkoSQII
通讯作者：
F. Lattanzio;Robert;Schlattererl;Michael Nicart;Kevin;Campbell;John L. SutkoSQII
DOI：
10.1016/s0021-9258(19)75701-9
发表时间：
1987-02
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
M. Inui;A. Saito;S. Fleischer
通讯作者：
M. Inui;A. Saito;S. Fleischer
影响因子：
3.6
作者：
I. Pessah;R. Stambuk;J. Casida
通讯作者：
I. Pessah;R. Stambuk;J. Casida
肌醇三硫代磷酸酯在分离的兔骨骼肌三联体中释放 Ca2+。
影响因子：
3.4
作者：
Valdivia,C;Valdivia,HH;Potter,BV;Coronado,R
通讯作者：
Coronado,R