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 Kv2.1 and Kv2.2, 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 Kv4.2, 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 Kv4.2 channels. In contrast, Stromatoxin-1 has no effect on Kv1.1, Kv1.2, Kv1.3, Kv1.4, Kv1.5, Kv1.6 or Kv3.4 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.