Valdivia H H, Kirby M S, Lederer W J, Coronado R
Department of Physiology, University of Wisconsin School of Medicine, Madison 53706.
Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12185-9. doi: 10.1073/pnas.89.24.12185.
We report the purification of two peptides, called "imperatoxin inhibitor" and "imperatoxin activator," from the venom of the scorpion Pandinus imperator targeted against ryanodine receptor Ca(2+)-release channels. Imperatoxin inhibitor has a M(r) of approximately 10,500, inhibits [3H]ryanodine binding to skeletal and cardiac sarcoplasmic reticulum with an ED50 of approximately 10 nM, and blocks openings of skeletal and cardiac Ca(2+)-release channels incorporated into planar bilayers. In whole-cell recordings of cardiac myocytes, imperatoxin inhibitor decreased twitch amplitude and intracellular Ca2+ transients, suggesting a selective blockade of Ca2+ release from the sarcoplasmic reticulum. Imperatoxin activator has a M(r) of approximately 8700, stimulates [3H]ryanodine binding in skeletal but not cardiac sarcoplasmic reticulum with an ED50 of approximately 6 nM, and activates skeletal but not cardiac Ca(2+)-release channels. These ligands may serve to selectively "turn on" or "turn off" ryanodine receptors in fragmented systems and whole cells.
我们报道了从帝王蝎毒液中纯化出两种肽，分别称为“imperatoxin抑制剂”和“imperatoxin激活剂”，它们作用于兰尼碱受体钙离子释放通道。Imperatoxin抑制剂的相对分子质量约为10500，抑制[³H]兰尼碱与骨骼肌和心肌肌浆网的结合，半数有效剂量（ED50）约为10 nM，并阻断整合到平面双层膜中的骨骼肌和心肌钙离子释放通道的开放。在心肌细胞的全细胞记录中，imperatoxin抑制剂降低了收缩幅度和细胞内钙离子瞬变，表明其对肌浆网钙离子释放具有选择性阻断作用。Imperatoxin激活剂的相对分子质量约为8700，刺激[³H]兰尼碱与骨骼肌而非心肌肌浆网的结合，ED50约为6 nM，并激活骨骼肌而非心肌的钙离子释放通道。这些配体可能用于在破碎系统和全细胞中选择性地“开启”或“关闭”兰尼碱受体。
