pandinotoxin pandinotoxin pandinotoxins are toxins from the venom of the emperor scorpion pandinus imperator. they are selective blockers of voltage-gated potassium channels pandinotoxinschematic diagram of the three-dimensional of pandinotoxinidentifiersorganismpandinus imperatorsymboln/a sources the source for the pandinotoxins is the venom of the scorpion pandinus imperator. chemistry family the toxins of the family are designated pandinotoxin (pitx)-kα, pitx-kβ, and pitx-kγ they are members of the α-ktx family of scorpion toxins. structure and homology the sequences of pandinotoxins ctx zftnvscttske-cwsvcqrlhntsr-gkcmnkkcrcys pitxk- α ---tisctnpkq-cyphckketgypn-akcmnrkckcfgr pitxk- β ---tisctnekq-cyphckketgypn-akcmnrkckcfgr pitx-k γ ---lvkcrgtsd-cgrpcqqqtgcpn-skcinrmckcygc figure 1: sequence of pandinotoxins. adapted from solution structure for pandinus toxin k-r (pitx-kr) pandinotoxin kα and -β the amino acid sequences of pitx-k α and pitx-k β are identical, except for the seventh amino acid: a proline in pitx-kα and a glutamic acid in pitx-kβ (see fig.1). pitx-kα and pitx-kβ are 35-residue peptides, which are found to have an α-helix from residues 10 to 21 and two β-sheets (β 1 is from residues 26-28, β 2 is from residues 33-35). one face of the α-helix is anchored to the β-sheet by three disulfide bonds which are conserved in all members of the charybdotoxin family (r-k toxins). pitx-k α and pitx-k β have only two β-sheets whereas other members of the family have three additional amino acid residues at the n-terminal portion, which forms a third β-sheet. pandinotoxin kγ pandinotoxin kγ has not yet been investigated. target 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) and they can reversibly block the shaker b potassium-channels (kv1.1 sub-family). mode of action 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 α and pitx-k β. 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-kα and ctx result in a higher affinity for a-type channels for pitx-kα. the affinity for the shaker b k+ channel is significantly smaller for pitx-kβ in comparison with pitx-kα owing to the changes in the seventh residue. therapeutic use intraplantarly injection of pitx-kα 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-kα almost completely eliminates diclofenac-induced anti-nociception.