JZTX-XIII, a Kv channel gating modifier toxin from Chinese tarantula Chilobrachys jingzhao.

Jingzhaotoxin-XIII (JZTX-XIII), a 35 residue polypeptide, with the ability to inhibit voltage-dependent potassium channels in the shab (Kv2) and shal (Kv4) subfamilies, was purified from the venom of the Chinese tarantula Chilobrachys jingzhao. Electrophysiological recordings carried out in Xenopus laevis oocytes showed that JZTX-XIII acted as gating modifier of voltage-dependent K+ channels which inhibited the Kv2.1 channel and Kv4.1 channel, with the IC50 value of 0.47 μM and 1.17 μM, respectively. JZTX-XIII shares high sequence similarity with gating modifier toxins inhibiting a wide variety of ion channels including Nav1.5 subtype, but it showed no Nav1.5 channel activity. Structure-function analysis indicates that the acidic residues of Glu10 and Glu17 in JZTX-XIII might be responsible for the loss of the Nav1.5 channel inhibitory potency for JZTX-XIII.