Scorpion Toxins Targeted Against the Sarcoplasmic Reticulum Ca2+- Release Channel of Skeletal and Cardiac Muscle

• Published in: Proceedings of the National Academy of Sciences - PNAS 1992-12, Vol.89 (24), p.12185-12189
• Main Authors: Valdivia, Hector H., Kirby, Mark S., Lederer, W. Jonathan, Coronado, Roberto
• Format: Article
• Language: English
• Subjects: Aminoacids, peptides. Hormones. Neuropeptides; Analytical, structural and metabolic biochemistry; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Ligands; Myocardium; Physiology; Protein isoforms; Proteins; Receptors; Sarcoplasmic reticulum; Scorpions; Toxins; Ungulates; Venoms
• ISSN: 0027-8424; 1091-6490
• 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 Ca2+-release channels. Imperatoxin inhibitor has a Mrof ≈ 10,500, inhibits [3H]ryanodine binding to skeletal and cardiac sarcoplasmic reticulum with an ED50of ≈ 10 nM, and blocks openings of skeletal and cardiac Ca2+-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 Mrof ≈ 8700, stimulates [3H]ryanodine binding in skeletal but not cardiac sarcoplasmic reticulum with an ED50of ≈ 6 nM, and activates skeletal but not cardiac Ca2+-release channels. These ligands may serve to selectively "turn on" or "turn off" ryanodine receptors in fragmented systems and whole cells.