title: Tityustoxin K alpha blocks voltage-gated noninactivating K+ channels and unblocks inactivating K+ channels blocked by alpha-dendrotoxin in synaptosomes.
abstract: Two nonhomologous polypeptide toxins, tityustoxin K alpha (TsTX-K alpha) and tityustoxin K beta (TsTX-K beta), purified from the venom of the Brazilian scorpion Tityus serrulatus, selectively block voltage-gated noninactivating K+ channels in synaptosomes (IC50 values of 8 nM and 30 nM, respectively). In contrast, alpha-dendrotoxin (alpha-DTX) and charybdotoxin (ChTX) block voltage-gated inactivating K+ channels in synaptosomes (IC50 values of 90 nM and 40 nM, respectively). We studied interactions among these toxins in 125I-alpha-DTX binding and 86Rb efflux experiments. Both TsTX-K alpha and ChTX completely displaced specifically bound 125I-alpha-DTX from synaptic membranes, but TsTX-K beta had no effect on bound alpha-DTX. TsTX-K alpha and TsTX-K beta blocked the same noninactivating component of 100 mM K(+)-stimulated 86Rb efflux in synaptosomes. Both alpha-DTX and ChTX blocked the same inactivating component of the K(+)-stimulated 86Rb efflux in synaptosomes. Both the inactivating and the noninactivating components of the 100 mM K(+)-stimulated 86Rb efflux were completely blocked when 200 nM TsTX-K beta and either 600 nM alpha-DTX or 200 nM ChTX were present. The effects of TsTX-K alpha and ChTX on 86Rb efflux were also additive. When TsTX-K alpha was added in the presence of alpha-DTX, however, only the noninactivating component of the K(+)-stimulated efflux was blocked. The inactivating component could then be blocked by ChTX, which is structurally homologous to TsTX-K alpha. We conclude that TsTX-K alpha unblocks the voltage-gated inactivating K+ channels in synaptosomes when they are blocked by alpha-DTX, but not when they are blocked by ChTX. TsTX-K alpha binds to a site on the inactivating K+ channel that does not occlude the pore; its binding apparently prevents alpha-DTX (7054 Da), but not ChTX (4300 Da), from blocking the pore. The effects of TsTX-K alpha on 125I-alpha-DTX binding and 86Rb efflux are mimicked by noxiustoxin, which is homologous to TsTX-K alpha and ChTX.
authors.affiliation: Department of Physiology, University of Maryland School of Medicine, Baltimore.
authors.forename: R S
authors.initials: RS
authors.lastname: Rogowski
authors.forename: B K
authors.initials: BK
authors.lastname: Krueger
authors.forename: J H
authors.initials: JH
authors.lastname: Collins
authors.forename: M P
authors.initials: MP
authors.lastname: Blaustein
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D018999:Charybdotoxin; D004347:Drug Interactions; D004546:Elapid Venoms / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects*; D008969:Molecular Sequence Data; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D012414:Rubidium Radioisotopes / Q000378:metabolism; D012604:Scorpion Venoms / Q000494:pharmacology*; D017386:Sequence Homology, Amino Acid; D013574:Synaptosomes / Q000378:metabolism*; D014118:Toxins, Biological / Q000494:pharmacology*
chemical_list: D004546:Elapid Venoms; D015221:Potassium Channels; D012414:Rubidium Radioisotopes; D012604:Scorpion Venoms; D014118:Toxins, Biological; D018999:Charybdotoxin; C003609:tityustoxin; C052567:noxiustoxin