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AsKC11, a Kunitz peptide from Anemonia sulcata, is a novel activator of G protein-coupled inward-rectifier potassium channels
An, D.; Pinheiro-Junior, E.L.; Béress, L.; Gladkikh, I.; Leychenko, E.; Undheim, E.A.B.; Peigneur, S.; Tytgat, J. (2022). AsKC11, a Kunitz peptide from Anemonia sulcata, is a novel activator of G protein-coupled inward-rectifier potassium channels. Mar. Drugs 20(2): 140. https://dx.doi.org/10.3390/md20020140
In: Marine Drugs. Molecular Diversity Preservation International (MDPI): Basel. ISSN 1660-3397; e-ISSN 1660-3397
|   |
| Trefwoorden |
Anemonia sulcata (Pennant, 1777) [WoRMS]
Marien/Kust |
| Author keywords |
sea anemone venom; AsKC11; GIRK1/2; potassium channels; brain diseases |
| Auteurs | | Top |
- An, D.
- Pinheiro-Junior, E.L.
- Béress, L.
- Gladkikh, I.
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- Leychenko, E.
- Undheim, E.A.B.
- Peigneur, S.
- Tytgat, J.
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| Abstract |
(1) Background: G protein-coupled inward-rectifier potassium (GIRK) channels, especially neuronal GIRK1/2 channels, have been the focus of intense research interest for developing drugs against brain diseases. In this context, venom peptides that selectively activate GIRK channels can be seen as a new source for drug development. Here, we report on the identification and electrophysiological characterization of a novel activator of GIRK1/2 channels, AsKC11, found in the venom of the sea anemone Anemonia sulcata. (2) Methods: AsKC11 was purified from the sea anemone venom by reverse-phase chromatography and the sequence was identified by mass spectrometry. Using the two-electrode voltage-clamp technique, the activity of AsKC11 on GIRK1/2 channels was studied and its selectivity for other potassium channels was investigated. (3) Results: AsKC11, a Kunitz peptide found in the venom of A. sulcata, is the first peptide shown to directly activate neuronal GIRK1/2 channels independent from Gi/o protein activity, without affecting the inward-rectifier potassium channel (IRK1) and with only a minor effect on KV1.6 channels. Thus, AsKC11 is a novel activator of GIRK channels resulting in larger K+ currents because of an increased chord conductance. (4) Conclusions: These discoveries provide new insights into a novel class of GIRK activators. |
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