CHARACTERIZATION OF PO1, A NEW PEPTIDE LIGAND OF THE APAMIN-SENSITIVECA2+ ACTIVATED K+ CHANNEL

A new peptide ligand of the small conductance Ca2+ activated Kf channe ls has been purified from the venom (obtained by manual rather than el ectrical stimulation of the scorpion Androctonus mauretanicus mauretan icus), by following the inhibition of the I-125-apamin binding to its receptor on rat brain synaptosomes. Only one step on a C-18 reversed-p hase high-performance liquid chromatography column was necessary to ob tain PO1. Its K-0.5 for the apamin binding site was 100 nM. The amino acid sequence of PO1 is different from those of leiurotoxin and PO5. F or the first time the same peptide was also purified from the venoms o f two other species of North African scorpions, Androctonus australis and Buthus occitanus tunetanus. PO1 was chemically synthesized by the solid-phase technique and fully characterized. A model of PO1 was cons tructed by amino acid replacement using PO5 nuclear magnetic resonance studies as the starting model. Structure-activity relationships betwe en these toxins and their receptor are discussed. (C) Munksgaard 1996.