Pandinotoxins are toxins from the venom of the emperor scorpion Pandinus imperator. They are selective blockers of voltage-gated potassium channels
The source for the pandinotoxins is the venom of the scorpion Pandinus imperator.
The toxins of the family are designated pandinotoxin (PiTX)-Kñ, PiTX-Kò, and PiTX-Kó They are members of the ñ-KTx family of scorpion toxins.
The amino acid sequences of PiTX-K ñ and PiTX-K ò are identical, except for the seventh amino acid: a proline in PiTX-Kñ and a glutamic acid in PiTX-Kò (see Fig.1).
PiTX-Kñ and PiTX-Kò are 35-residue peptides, which are found to have an ñ-helix from residues 10 to 21 and two ò-sheets (ò 1 is from residues 26-28, ò 2 is from residues 33-35). One face of the ñ-helix is anchored to the ò-sheet by three disulfide bonds which are conserved in all members of the charybdotoxin family (R-K toxins). PiTX-K ñ and PiTX-K ò have only two ò-sheets whereas other members of the family have three additional amino acid residues at the N-terminal portion, which forms a third ò-sheet.
Pandinotoxin Kó has not yet been investigated.
Pandinotoxins are the most potent inhibitors of the rapidly inactivating A-type voltage-gated potassium channels. They also block the delayed rectifier, slowly inactivating channels of the subfamily A member 2 (Kv1.2/KCNA2) [1] and they can reversibly block the shaker B potassium-channels (Kv1.1 sub-family).
The residue K27, a lysine at place 27 of the protein sequence, interacts with the voltage sensitivity blocking activity of CTX channels. It is conserved among PiTX-K ñ and PiTX-K ò. This amino acid is located nearby the selectivity filter of the pore and it is responsible for the interaction with A-type channels by being inserted in the pore of the ion channels. The structural differences in the backbone and side chain between PiTX-Kñ and CTX result in a higher affinity for A-type channels for PiTX-Kñ. The affinity for the Shaker B K<sup>+</sup> channel is significantly smaller for PiTX-Kò in comparison with PiTX-Kñ owing to the changes in the seventh residue.
Intraplantarly injection of PiTX-Kñ before or after the administration of diclofenac produces a significant reduction in spontaneous flinching, mechanical allodynia and thermal hyperalgesia in a rat model for bone cancer. Downregulation of PiTX-Kñ almost completely eliminates diclofenac-induced anti-nociception.