title: Scorpion toxins targeted against the sarcoplasmic reticulum Ca(2+)-release channel of skeletal and cardiac muscle.
abstract: 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.
authors.affiliation: Department of Physiology, University of Wisconsin School of Medicine, Madison 53706.
authors.forename: H H
authors.initials: HH
authors.lastname: Valdivia
authors.forename: M S
authors.initials: MS
authors.lastname: Kirby
authors.forename: W J
authors.initials: WJ
authors.lastname: Lederer
authors.forename: R
authors.initials: R
authors.lastname: Coronado
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000502:physiology; D015220:Calcium Channels / Q000187:drug effects*; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D008024:Ligands; D009206:Myocardium; D010455:Peptides / Q000494:pharmacology; D011817:Rabbits; D011950:Receptors, Cholinergic / Q000187:drug effects*; D019837:Ryanodine Receptor Calcium Release Channel; D012519:Sarcoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D012604:Scorpion Venoms / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D015220:Calcium Channels; D008024:Ligands; D010455:Peptides; D011950:Receptors, Cholinergic; D019837:Ryanodine Receptor Calcium Release Channel; D012604:Scorpion Venoms; D002118:Calcium