8.B.26 The Scorpion Toxin, Scoloptoxin (Scoloptoxin) Family  

The Scoloptoxin family includes a number of peptide/protein toxins of vaious sized that bind to and inhibit various Na⁺ and K⁺ channels of the VIC superfamily (1.A.1).  For example, κ-scoloptoxin, Ssm1a, inhibits voltage-gated potassium channel currents in DRG neurons with an IC₅₀ of 44.2 nM and shows signs of neurotoxicity including twitching, paralysis, and body contractions (Yang et al. 2012), and the 47 aa centipede toxin, Ssd609, inhibits K⁺ currents by binding to KCNE1 (8.A.10.1.1), a single-span transmembrane auxiliary protein that modulates the voltage-gated potassium channel KCNQ1 (TC# 1.A.1.15.1 and 1.A.1.15.6). The KCNQ1/KCNE1 complex in cardiomyocytes exhibited slow activated potassium (Iks) currents (Sun et al. 2015). Another centipede toxin, SsmTx-I acts as a simple inhibitor or channel blocker rather than a gating modifier of at least 9 channels including Kv2.1 (TC# 1.A.1.2.11) (Chen et al. 2014). The high resolution structures of several of these toxins are known.