Fast K+ currents from cerebellum granular cells are completely blocked by a peptide purified from Androctonus australis Garzoni scorpion venom

Abstract

A novel peptide was purified from the venom of the scorpion Androctonus australis Garzoni (abbreviated Aa1, corresponding to the systematic number alpha KTX4.4). It contains 37 amino acid residues, has a molecular mass of 3850 Da, is closely packed by three disulfide bridges and a blocked N-terminal amino acid. This peptide selectively affects the K(+) currents recorded from cerebellum granular cells. Only the fast activating and inactivating current, with a kinetics similar to I(A)-type current, is completely blocked by the addition of low micromolar concentrations (K(i) value of 150 nM) of peptide Aa1 to the external side of the cell preparation. The blockade is partially reversible in our experimental conditions. Aa1 blocks the channels in both the open and the closed states. The blockage is test potential independent and is not affected by changes in the holding potential. The kinetics of the current are not affected by the addition of Aa1 to the preparation; it means that the block is a simple 'plugging mechanism', in which a single toxin molecule finds a specific receptor site in the external vestibule of the K(+) channel and thereby occludes the outer entry to the K(+) conducting pore.

Potassium Channels Blockers from the Venom ofAndroctonus mauretanicus mauretanicus

“…The first member of the α -KTx 15 subfamily characterized was Aa1 from the Androctonus australis venom (3869 Da) [46]. At the primary sequence level, the toxin has an unusual N-terminal pyroglutamic acid, like Charybdotoxin and Iberiotoxin, but the rest of its sequence was totally original.…”

“…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 .…”

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

“…Recently, Aa1, a new blocker of fast K + currents from cerebellum granular cells was isolated from the venom of the scorpion Androctonus australis [5]. Here, we describe the chemistry, the pharmacology and the rat brain binding sites distribution of a Buthus martensi Karch scorpion toxin, BmTX3, which blocks an A‐type current in neurons of striatum cells in culture.…”

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.…”