Peptide toxins as probes of ryanodine receptor structure and function.

Toxins from scorpion venom are emerging as useful ligands for structure/function studies of ryanodine receptors (RyR), the sarcoplasmic reticulum Ca(2+) release channels that elevate intracellular Ca(2+) to elicit contraction of cardiac and skeletal muscle. Imperatoxin A (IpTx(a)), a 3.7 kDa peptide from the African scorpion P. imperator, is an agonist of RyRs which, similar to the alkaloid ryanodine, binds with high affinity to the RyR protein and induces the appearance of a long-lived subconductance state. Imperatoxin I (IpTx(i)), a 15 kDa heterodimeric protein from the same venom that displays phospholipase A(2) activity, inhibits RyRs without a physical interaction with the channel protein, by releasing free fatty acids into the incubation medium. IpTx(a) and IpTx(i) are the first of a group of peptide probes of RyRs with diverse mechanism of action which overcome some of the undesirable characteristics of ryanodine.