THE CARDIAC SARCOPLASMIC-RETICULUM CALCIUM-RELEASE CHANNEL - MODULATION OF RYANODINE BINDING AND SINGLE-CHANNEL ACTIVITY
THE CARDIAC SARCOPLASMIC-RETICULUM CALCIUM-RELEASE CHANNEL - MODULATION OF RYANODINE BINDING AND SINGLE-CHANNEL ACTIVITY
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DOI：
10.1016/0005-2736(90)90113-3
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发表时间：
1990-02-28
期刊：
影响因子：
--
通讯作者：
WILLIAMS, AJ
中科院分区：
文献类型：
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作者：
HOLMBERG, SRM;WILLIAMS, AJ
[3 H]Ryanodine与离体心肌肌浆网制剂的结合已被研究。报道了一种产生非常高水平的特异性结合的方法。Scatchard分析高达50 nM兰尼碱的结合产生的数据推断出一类结合位点，Kd为1.4 nM，Bmax为9.7 pmol/mg蛋白质。微摩尔钙是主要的活化配体，其对结合的影响是由配体调节的，这些配体类似地影响掺入人工平面磷脂双层的单个钙释放通道的活性。苯并咪唑类药物舒马唑在亚活化钙浓度存在下能够刺激兰尼定结合。兰尼碱仅在天然通道处于开放状态时与其结合，并且通过不足以产生完全单通道激活的配体实现最大兰尼碱结合的刺激。提出了一个模型，它涉及到的兰尼定绑定的行为的单通道的调制。
[3H]Ryanodine binding to a preparation of isolated cardiac sarcoplasmic reticulum has been investigated. A method is reported which produces a very high level of specific binding. Scatchard analysis of binding up to 50 nM ryanodine yields data which infer a single class of binding sites with a Kd of 1.4 nM and a Bmax of 9.7 pmol/mg protein. Micromolar calcium is the principal activating ligand and its effects on binding are modulated by ligands which similarly affect the activity of single calcium-release channels incorporated into artificial planar phospholipid bilayers. The benzimidazole drug, sulmazole, is able to stimulate ryanodine binding in the presence of sub-activating calcium concentrations. Ryanodine binds to the native channel only when it is in its open state and stimulation of maximal ryanodine binding is achieved by ligands which are insufficient to produce full single-channel activation. A model is proposed which relates the modulation of ryanodine binding to the behaviour of single channels.