A new class of scorpion toxin binding sites related to an A‐type K⁺ channel: pharmacological characterization and localization in rat brain

Abstract

A new scorpion toxin (3751.8 Da) was isolated from the Buthus martensi venom, sequenced and chemically synthesized (sBmTX3). The A-type current of striatum neurons in culture completely disappeared when 1 W WM sBmTX3 was applied (K d = 54 nM), whereas the sustained K + current was unaffected. 125 I-sBmTX3 specifically bound to rat brain synaptosomes (maximum binding = 14 fmol mg^1 of protein, K d = 0.21 nM). A panel of toxins yet described as specific ligands for K + channels were unable to compete with 125 I-sBmTX3. A high density of 125 I-sBmTX3 binding sites was found in the striatum, hippocampus, superior colliculus, and cerebellum in the adult rat brain. ß 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.

Potassium Channels Blockers from the Venom ofAndroctonus mauretanicus mauretanicus

“…Autoradiograms of adult rat brain sections demonstrated a highly heterogeneous distribution of 125 I-BmTX3 binding sites throughout the adult rat brain. High density of receptors was found in the striatum, the CA1 and CA3 field of the hippocampus, the superior colliculus, and in the granular layer of the cerebellum [47]. We then purified AmmTX3 (3827 Da), an analog of Aa1 and BmTX3, from the venom of Androctonus mauretanicus mauretanicus [22].…”

“…Aa1 [46], AaTX1, and AaTX2 [48] are from Androctonus australis ; BmTX3 [47] is from Buthus martensii ; AmmTX3 [22] is from Androctonus mauretanicus ; AamTX [49] is from Androctonus amoreuxi . Discrepin [54] is from the Venezuelan scorpion Tityus discrepans .…”

Kv4 potassium channels modulate hippocampal EPSP-spike potentiation and spatial memory in rats

“…Recently, three "shortchain" scorpion toxins, Aa1 from Androctonus australis, BmTX3 from Buthus martensi, and AmmTX3 from Androctonus mauretanicus (Pisciotta et al 2000;Vacher et al 2001Vacher et al , 2004 have been described as specific blockers of Kv4 channels. Binding and displacement experiments using rat brain synaptosomes showed that AmmTX3 and Aa1 competed effectively with 125 I-labeled sBmTX3 binding.…”

Expanding the scorpion toxin α‐KTX 15 family with AmmTX3 from Androctonus mauretanicus

“…Two new toxins blocking transient A‐currents were recently isolated from scorpion venoms: Aa1, from Androctonus australis , which was shown to block an A‐type K + channels in cerebellar granular cells [7] and BmTX3, from Buthus martensi Karch, which was found to block an A‐type current in striatal neurons in culture. These toxins revealed a new class of scorpion toxin binding sites in rat brain [8].…”