IpTxa acts on the Ryanodine receptors (RyR), which are intracellular Ca2+ release channels mainly known for their role in regulating Ca2+ release from the sarcoplasmatic reticulum of striated muscles.[2] The peptide acts better on RyR type 1 than on type 3. RyR type 2 seems to be insensitive to IpTxa.[3]
The part of the peptide that looks like the II-III loop of the (DHPR) binds directly to RyR and enhances ryanodine binding to trigger Ca2+ release.[3]
The toxin comes from the venom of the African scorpion Pandinus imperator.[1] The structure of IpTxi consists of:
Two polypeptides. A large subunit of 104 amino acids (sequence TMWGTKWCGSGNEATDISELGYWSNLDSCCRTHDHCDNIPSGQTKYGLTNEGKYTMMNCKCETAFEQCLRNVTGGMEGPAAGFVRKTYFDLYGNGCYNVQCPSQ) and a smaller one of 27 amino acids (sequence SEECPDGVATYTGEAGYGAWAINKLNG).
Subunits are linked by a disulfide bond.
Phospholipase A2 (PLA2) activity on the large subunit.
When an action potential reaches the muscle, RyR channels open and Ca2+ becomes available in the cell to induce contraction. The presence of Ca2+ induces the large subunit of IpTxitohydrolyze the Sn2 fatty acyl bond from the membrane of the sarcoplasmatic reticulum. This process is executed by PLA2 activity. The freed fatty acids bind to the RyR itself or to a closely associated protein linked to gating. Binding of the RyR induces blocking of the channel. When the concentration of free fatty acids is low there will be an incomplete block of RyR; higher concentrations will give a complete block.[4]
Because IpTxi also works on the RyR channels of the heart muscles, it could potentially be used as a drug against arrhythmia. This has not yet been proven, and must be studied in vivo first.[5]
