Heteroscodratoxin-1

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).

[3] Heteroscodratoxin-1 inhibits subtypes of both delayed rectifier (KV2.1 and KV2.2) and A-type rapidly inactivating (KV4.1, KV4.2 and KV4.3) voltage-gated potassium channels.

[4] It is thought that heteroscodratoxin-1 modifies gating of specific potassium channels by shifting the activation threshold to more positive values.

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 mice, however, it has been found that intracerebroventricular injection of 500 pmol HmTx1 induces convulsions, spasms, tremors and death within 1 hour.