Stromatoxin-1 / ScTx1

Stromatoxin-1 (ScTx-1) has been isolated from the venom of the African tarentula Stromatopelma calceata.Stromatoxin-1 is a 34 amino-acid long peptide that belongs to the structural family of inhibitor cystine knot peptides reticulated by three disulfide bridges. It has an amidated C-terminus and bears strong homology with hanatoxin 1 (83%).Stromatoxin-1 inhibits with high affinities K_v2.1 and K_v2.2, that encode delayed K⁺ channels (respectively, with IC₅₀ of 12 and 21 nM). The block is voltage-dependent and slowly reversible. Stromatoxin-1 is also a very sensitive inhibitor of K_v4.2, that encodes a transient K⁺ current (IC₅₀ of 1.2 nM). Here also, the block is voltage-dependent indicating that ScTx-1 acts as a gating modifier rather than a pore blocker. Reversibility is faster on K_v4.2 channels. In contrast,Stromatoxin-1 has no effect on K_v1.1, K_v1.2, K_v1.3, K_v1.4, K_v1.5, K_v1.6 or K_v3.4 channels. The toxin has also no effect on voltage-dependent Na⁺ and Ca²⁺ channels of cerebellar granule cells. Stromatoxin-1 was found to increase the spontaneous phasic contraction amplitude, muscle force and tone in isolated rat urinary bladder smooth muscle. It also enhances myogenic constriction in pressurized arterial segments.