Tityustoxin-Kα, a structurally novel and highly potent K+ channel peptide toxin, interacts with the α-dendrotoxin binding site on the cloned Kv1.2 K+ channel

T. R. Werkman, T. A. Gustafson, R. S. Rogowski, M. P. Blaustein, Michael A Rogawski

Research output: Contribution to journalArticle

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Abstract

The interaction between two nonhomologous K+ channel toxins, Tityus serrulatus (scorpion) toxin tityustoxin-Kα (TsTX-Kα) and Dendroaspis angusticeps (snake) toxin dendrotoxin (α-DTX), was investigated on K+ currents in B82 fibroblast cells transformed to express the Kv1.2 K+ channel. As demonstrated previously, α-DTX was a potent blocker of the K+ current (Kd, 2.8 nM). Recombinant TsTX-Kα produced a similar block of the current but was 1 order of magnitude more potent (Kd, 0.21 nM). TsTX-Kα did not affect the kinetic properties of the current or its voltage dependence of activation. Experiments with excised and cell-attached patch recordings demonstrated that TsTX-Kα blocks the K+ channel by binding to an extracellular site. In the presence of TsTX-Kα the blocking potency of α-DTX was reduced, whereas the potency of 4-aminopyridine, which also blocks the channel, was unaffected. α-DTX caused a rightward shift in the scaled concentration-response curve for TsTX-Kα, the magnitude of which was reasonably well predicted by a model in which there is a competitive interaction between the two peptide toxins. We conclude that TsTX-Kα and α-DTX block the Kv1.2 K+ channel by binding to the same or closely related sites.

Original languageEnglish (US)
Pages (from-to)430-436
Number of pages7
JournalMolecular Pharmacology
Volume44
Issue number2
StatePublished - Aug 1993
Externally publishedYes

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Kv1.2 Potassium Channel
Binding Sites
Scorpions
Elapidae
4-Aminopyridine
Peptides
Snakes
Fibroblasts
tityustoxin
dendrotoxin

ASJC Scopus subject areas

  • Pharmacology

Cite this

Tityustoxin-Kα, a structurally novel and highly potent K+ channel peptide toxin, interacts with the α-dendrotoxin binding site on the cloned Kv1.2 K+ channel. / Werkman, T. R.; Gustafson, T. A.; Rogowski, R. S.; Blaustein, M. P.; Rogawski, Michael A.

In: Molecular Pharmacology, Vol. 44, No. 2, 08.1993, p. 430-436.

Research output: Contribution to journalArticle

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abstract = "The interaction between two nonhomologous K+ channel toxins, Tityus serrulatus (scorpion) toxin tityustoxin-Kα (TsTX-Kα) and Dendroaspis angusticeps (snake) toxin dendrotoxin (α-DTX), was investigated on K+ currents in B82 fibroblast cells transformed to express the Kv1.2 K+ channel. As demonstrated previously, α-DTX was a potent blocker of the K+ current (Kd, 2.8 nM). Recombinant TsTX-Kα produced a similar block of the current but was 1 order of magnitude more potent (Kd, 0.21 nM). TsTX-Kα did not affect the kinetic properties of the current or its voltage dependence of activation. Experiments with excised and cell-attached patch recordings demonstrated that TsTX-Kα blocks the K+ channel by binding to an extracellular site. In the presence of TsTX-Kα the blocking potency of α-DTX was reduced, whereas the potency of 4-aminopyridine, which also blocks the channel, was unaffected. α-DTX caused a rightward shift in the scaled concentration-response curve for TsTX-Kα, the magnitude of which was reasonably well predicted by a model in which there is a competitive interaction between the two peptide toxins. We conclude that TsTX-Kα and α-DTX block the Kv1.2 K+ channel by binding to the same or closely related sites.",
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T1 - Tityustoxin-Kα, a structurally novel and highly potent K+ channel peptide toxin, interacts with the α-dendrotoxin binding site on the cloned Kv1.2 K+ channel

AU - Werkman, T. R.

AU - Gustafson, T. A.

AU - Rogowski, R. S.

AU - Blaustein, M. P.

AU - Rogawski, Michael A

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N2 - The interaction between two nonhomologous K+ channel toxins, Tityus serrulatus (scorpion) toxin tityustoxin-Kα (TsTX-Kα) and Dendroaspis angusticeps (snake) toxin dendrotoxin (α-DTX), was investigated on K+ currents in B82 fibroblast cells transformed to express the Kv1.2 K+ channel. As demonstrated previously, α-DTX was a potent blocker of the K+ current (Kd, 2.8 nM). Recombinant TsTX-Kα produced a similar block of the current but was 1 order of magnitude more potent (Kd, 0.21 nM). TsTX-Kα did not affect the kinetic properties of the current or its voltage dependence of activation. Experiments with excised and cell-attached patch recordings demonstrated that TsTX-Kα blocks the K+ channel by binding to an extracellular site. In the presence of TsTX-Kα the blocking potency of α-DTX was reduced, whereas the potency of 4-aminopyridine, which also blocks the channel, was unaffected. α-DTX caused a rightward shift in the scaled concentration-response curve for TsTX-Kα, the magnitude of which was reasonably well predicted by a model in which there is a competitive interaction between the two peptide toxins. We conclude that TsTX-Kα and α-DTX block the Kv1.2 K+ channel by binding to the same or closely related sites.

AB - The interaction between two nonhomologous K+ channel toxins, Tityus serrulatus (scorpion) toxin tityustoxin-Kα (TsTX-Kα) and Dendroaspis angusticeps (snake) toxin dendrotoxin (α-DTX), was investigated on K+ currents in B82 fibroblast cells transformed to express the Kv1.2 K+ channel. As demonstrated previously, α-DTX was a potent blocker of the K+ current (Kd, 2.8 nM). Recombinant TsTX-Kα produced a similar block of the current but was 1 order of magnitude more potent (Kd, 0.21 nM). TsTX-Kα did not affect the kinetic properties of the current or its voltage dependence of activation. Experiments with excised and cell-attached patch recordings demonstrated that TsTX-Kα blocks the K+ channel by binding to an extracellular site. In the presence of TsTX-Kα the blocking potency of α-DTX was reduced, whereas the potency of 4-aminopyridine, which also blocks the channel, was unaffected. α-DTX caused a rightward shift in the scaled concentration-response curve for TsTX-Kα, the magnitude of which was reasonably well predicted by a model in which there is a competitive interaction between the two peptide toxins. We conclude that TsTX-Kα and α-DTX block the Kv1.2 K+ channel by binding to the same or closely related sites.

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