Hm1b Toxin

δ-theraphotoxin-Hm1b (Hm1b) is a 34 amino acid peptidyl toxin originally isolated from the venom of the tarantula, Heteroscodra maculata¹. Hm1b acts as a potent and highly selective activator of the voltage-gated sodium (Na_V) 1.1 and Na_V1.3 channels. This toxin inhibits the inactivation of the human Na_V1.1 channel (expressed in HEK293 cells) with an EC  value of 12 nM^1,2.

The Hm1b toxin has a high level of sequence similarity to the Hm1a toxin, which is also a selective and specific activator of Na_V1.1 channels. Both toxins are members of the extended family of inhibitor cystine knot (ICK) peptides with C1–C4, C2–C5, and C3–C6 disulfide architecture. In addition, they share secondary structure characteristics, specifically an antiparallel β hairpin. Despite the high degree of sequence similarity between Hm1a and Hm1b, the latter is much more stable in biological fluids².

Na_V channels are involved in a wide array of physiological processes and play a fundamental role in normal neurological function, especially in the initiation and propagation of action potentials. Na_V1.1 channel has been utilized as a therapeutic target for various brain disorders, including epilepsy, Alzheimer's disease, and autism. The Na_V1.1 channel also contributes to mechanical pain by regulating the excitability of a specific subset of sensory neurons within the peripheral nervous system.