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Heteroscodratoxin-1 (also known as kappa-theraphototoxin Hm1a or HmTx1) is a neurotoxin produced by the venom glands of the Heteroscodra maculata (Togo starburst tarantula) that shifts the activation threshold of voltage-gated potassium channels to more positive potentials.

Source
Heteroscodratoxin-1 can be obtained from venom glands of the Heteroscodra maculata (Togo starburst tarantula or Togo starburst baboon spider).

Chemistry
Heteroscodratoxin-1 is a basic protein (isoelectric point of 7.69) composed of 35 amino acids with a carboxylated C-terminus. Its sequence shows strong similarity with other taruntala toxins such as Scodratoxin, Hanatoxin and SGTx1. Structurally the protein belongs to the huwentoxin-1 family of inhibitory spider peptides based on its knottin backbone that consists of three crossing disulfide bridges (Cys1-Cys4/Cys2-Cys5/Cys3-Cys6).

Target
Heteroscodratoxin-1 inhibits subtypes of both delayed rectifier (KV2.1/ KCNB1 and KV2.2/ KCNB2) and A type rapidly inactivating (KV4.1/ KCND1, KV4.2/ KCND2 and KV4.3/ KCND3) voltage-gated potassium channels. The amount of conductance depression evoked at 0 mV has been determined in COS cells: Conversely under the same experimental conditions no significant effect (defined as less than 20% inhibition at 300 nM) has been found on the currents through other A type rapidly inactivating (KV1.4 and KV3.4) or delayed rectifier potassium channels (KV1.1, KV1.2, KV1.3, KV1.5, KV1.6, KV1.2/ KV1.5, or KVLQT1). Sodium and calcium channels also seem unaffected as perfusion of rat granular cells with 100 nM heteroscodratoxin-1 does not change ion flow (less than 5% inhibition) accross the membrane at 0 mV.
 * 23% on KV2.1 at 100 nM
 * 19% on KV2.2 at 100 nM
 * 50% on KV4.1 at 280 nM
 * 39% on KV4.2 at 300 nM
 * 43% on KV4.3 at 300 nM.

Mode of action
It is thought that heteroscodratoxin-1 modifies gating of specific potassium channels by shifting the activation threshold to more positive values resulting in a decrease of current amplitude at a given potential. The mechanism underlying this modification has been largely elucidated using molecular docking simulation for the KV2.1 potassium channel which is highly expressed in mammalian neurons and interacts strongly with heteroscodratoxin-1. In this model the C-terminal residue of the KV2.1 S3-segment (S3C) serves as a binding site for Hmtx-1 forming both hydrophobic and hydrophilic bonds (van der Waals strength of 402.27 kcal/mol). Interaction between the toxin and the potassium channel induces a helical movement of S3C resulting in limited spatial freedom of the S4-segment which is responsible for channel gating.

Toxicity
Information on toxic effects of Heteroscodratoxin-1 in humans is not available. In mice however it has been found that intracerebroventricular injection of 500 pmol HmTx1 induces convulsions, spasms, tremors and death within 1 hour. At 100 pmol a less severe response develops though death still occurs after 2 hours.