AmmTX3

AmmTX3 is a peptide toxin identified from the venom of the scorpion Androctonus mauretanicus. AmmTX3 is a highly specific blocker of K_v4 channels, which selectively and almost completely blocks transient A-type K⁺ currents with a K_i of 131 nM. AmmTX3 induces epileptiform behaviors and causes death in mice receiving intracerebroventricular injection. AmmTX3 increases the excitability of dentate gyrus granule cells, reduces GABAergic inhibition, enhances and stabilizes the EPSP-spike component of long-term potentiation, and impairs reference memory. AmmTX3 can be used in research related to pain, epilepsy, and autism spectrum disorder^[1][2][3]. IC50 & Target:K_v4 channel^[2] In Vitro:AmmTX3 (1 h) binds with high affinity to a specific site on rat brain synaptosomes, fully displacing ¹²⁵I-labelled sBmTX3 with a K_i of 19.5 pM, and exhibits a K_d of 66 pM for its own binding site^[1].
AmmTX3 (0.1 nM-10 μM) potently blocks the A-type K⁺ current in primary striatal neurons in culture, with a K_i of 131 nM, and its inhibitory effect is reversible^[1].
AmmTX3 (0.5 μM) potently blocks Kv4.2 channel currents in CHO-K1 cells co-expressed with DPP6S (with or without KChIP1), but only weakly blocks Kv4.2 + KChIP1 currents, demonstrating DPP6S confers high AmmTX3 sensitivity to Kv4.2 channels^[3].
AmmTX3 (0.5 μM) potently blocks Kv4.3 channel currents in CHO-K1 cells co-expressed with DPP10a, but only weakly blocks Kv4.3 + KChIP1 currents, demonstrating DPP10a confers high AmmTX3 sensitivity to Kv4.3 channels^[3]. In Vivo:AmmTX3 (0.75 mg; i.c.v.; single injection) impairs spatial reference memory consolidation when administered during early stages of eight-arm radial maze training, causing a 1-day learning delay when injected after session 1 and increasing reference memory errors in session 4 when injected after session 3, with no effect on working memory^[2].
AmmTX3 (0.75 mg; i.c.v.; single injection) increases and stabilizes the EPSP-spike component of long-term potentiation in the dentate gyrus from 90 minutes post-high-frequency stimulation, with no effect on basal synaptic transmission or short-term plasticity^[2].