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

A novel peptide was purified from the venom of the scorpion Androctonus aus tralis Garzoni (abbreviated Aa1, corresponding to the systematic number alp ha KTX4.4). It contains 37 amino acid residues, has a molecular mass of 385 0 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 curren t, with a kinetics similar to I-A-type current, is completely blocked by th e addition of low micromolar concentrations (K-i value of 150 nM) of peptid e Aa I to the external side of the cell preparation. The blockade is partia lly reversible in our experimental conditions. Aa1 blocks the channels in b oth the open and the closed states. The blockage is test potential independ ent and is not affected by changes in the holding potential. The kinetics o f the current are not affected by the addition of Aa1 to the preparation; i t 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 pe n. (C) 2000 Elsevier Science B.V. All rights reserved.