Imperatoxin A (IpTxa) is a 33 amino acid natural peptidyl toxin isolated from the venom of scorpion Pandinus imperator. IpTxa interacts specifically and activates the sarcoplasmic reticulum Ca2+-release channel of skeletal and cardiac muscle (ryanodine receptor 1 and 2). It reversibly enhances binding of ryanodine to the receptors. The activating effect of IpTxa on skeletal ryanodine receptor is Ca2+-dependent, synergized by caffeine, and independent of other modulators of RyRs1-3.
IpTxa increased the open probability of rabbit skeletal muscle RyRs by increasing the frequency of open events and decreasing the duration of the closed lifetimes.2
IpTxa displays structural homology with an activating segment of the a1 subunit of the skeletal dihydropyridine receptor (II-III loop, segment Glu666-Leu690) which is putatively the native activator of ryanodine receptor. IpTxa and the segment Glu666-Leu690 activate RyRs in a similar manner and appear to compete for a common binding site on the ryanodine channel protein4. This suggest a common mechanism of IpTxa and dihydropyridine receptor for modulation of RyR4.
Imperatoxin-A (#STI-333) is a highly pure, synthetic, and biologically active peptide toxin.