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 language | English (US) |
|---|---|
| Pages (from-to) | 430-436 |
| Number of pages | 7 |
| Journal | Molecular Pharmacology |
| Volume | 44 |
| Issue number | 2 |
| State | Published - Aug 1993 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
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
PY - 1993/8
Y1 - 1993/8
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.
UR - http://www.scopus.com/inward/record.url?scp=0027327958&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027327958&partnerID=8YFLogxK
M3 - Article
C2 - 8355670
AN - SCOPUS:0027327958
VL - 44
SP - 430
EP - 436
JO - Molecular Pharmacology
JF - Molecular Pharmacology
SN - 0026-895X
IS - 2
ER -