AsKC11, a Kunitz Peptide from <i>Anemonia sulcata</i>, Is a Novel Activator of G Protein-Coupled Inward-Rectifier Potassium Channels
(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 n...
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| Format: | Article |
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MDPI AG
2022-02-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/20/2/140 |
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| author | Dongchen An Ernesto Lopes Pinheiro-Junior László Béress Irina Gladkikh Elena Leychenko Eivind A. B. Undheim Steve Peigneur Jan Tytgat |
| author_facet | Dongchen An Ernesto Lopes Pinheiro-Junior László Béress Irina Gladkikh Elena Leychenko Eivind A. B. Undheim Steve Peigneur Jan Tytgat |
| author_sort | Dongchen An |
| collection | DOAJ |
| description | (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 <i>Anemonia sulcata</i>. (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 <i>A. sulcata</i>, 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 K<sub>V</sub>1.6 channels. Thus, AsKC11 is a novel activator of GIRK channels resulting in larger K<sup>+</sup> currents because of an increased chord conductance. (4) Conclusions: These discoveries provide new insights into a novel class of GIRK activators. |
| first_indexed | 2024-03-09T21:33:40Z |
| format | Article |
| id | doaj.art-c30e3f24ff8f44c7821bc2c20af3c4bc |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-03-09T21:33:40Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-c30e3f24ff8f44c7821bc2c20af3c4bc2023-11-23T20:50:29ZengMDPI AGMarine Drugs1660-33972022-02-0120214010.3390/md20020140AsKC11, a Kunitz Peptide from <i>Anemonia sulcata</i>, Is a Novel Activator of G Protein-Coupled Inward-Rectifier Potassium ChannelsDongchen An0Ernesto Lopes Pinheiro-Junior1László Béress2Irina Gladkikh3Elena Leychenko4Eivind A. B. Undheim5Steve Peigneur6Jan Tytgat7Toxicology and Pharmacology, KU Leuven, Campus Gasthuisberg, O & N2, Herestraat 49, P.O. Box 922, 3000 Leuven, BelgiumToxicology and Pharmacology, KU Leuven, Campus Gasthuisberg, O & N2, Herestraat 49, P.O. Box 922, 3000 Leuven, BelgiumDepartment of Internal Medicine, Division Experimental and Clinical Peptide Research, Pharis Biotech GmbH/Medical School Hannover, Feodor-Lynen-Str. 31, 30625 Hannover, GermanyG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 690022 Vladivostok, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 690022 Vladivostok, RussiaCentre for Biodiversity Dynamics, Department of Biology, Norwegian University of Science and Technology, N-7491 Trondheim, NorwayToxicology and Pharmacology, KU Leuven, Campus Gasthuisberg, O & N2, Herestraat 49, P.O. Box 922, 3000 Leuven, BelgiumToxicology and Pharmacology, KU Leuven, Campus Gasthuisberg, O & N2, Herestraat 49, P.O. Box 922, 3000 Leuven, Belgium(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 <i>Anemonia sulcata</i>. (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 <i>A. sulcata</i>, 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 K<sub>V</sub>1.6 channels. Thus, AsKC11 is a novel activator of GIRK channels resulting in larger K<sup>+</sup> currents because of an increased chord conductance. (4) Conclusions: These discoveries provide new insights into a novel class of GIRK activators.https://www.mdpi.com/1660-3397/20/2/140sea anemone venomAsKC11GIRK1/2potassium channelsbrain diseases |
| spellingShingle | Dongchen An Ernesto Lopes Pinheiro-Junior László Béress Irina Gladkikh Elena Leychenko Eivind A. B. Undheim Steve Peigneur Jan Tytgat AsKC11, a Kunitz Peptide from <i>Anemonia sulcata</i>, Is a Novel Activator of G Protein-Coupled Inward-Rectifier Potassium Channels Marine Drugs sea anemone venom AsKC11 GIRK1/2 potassium channels brain diseases |
| title | AsKC11, a Kunitz Peptide from <i>Anemonia sulcata</i>, Is a Novel Activator of G Protein-Coupled Inward-Rectifier Potassium Channels |
| title_full | AsKC11, a Kunitz Peptide from <i>Anemonia sulcata</i>, Is a Novel Activator of G Protein-Coupled Inward-Rectifier Potassium Channels |
| title_fullStr | AsKC11, a Kunitz Peptide from <i>Anemonia sulcata</i>, Is a Novel Activator of G Protein-Coupled Inward-Rectifier Potassium Channels |
| title_full_unstemmed | AsKC11, a Kunitz Peptide from <i>Anemonia sulcata</i>, Is a Novel Activator of G Protein-Coupled Inward-Rectifier Potassium Channels |
| title_short | AsKC11, a Kunitz Peptide from <i>Anemonia sulcata</i>, Is a Novel Activator of G Protein-Coupled Inward-Rectifier Potassium Channels |
| title_sort | askc11 a kunitz peptide from i anemonia sulcata i is a novel activator of g protein coupled inward rectifier potassium channels |
| topic | sea anemone venom AsKC11 GIRK1/2 potassium channels brain diseases |
| url | https://www.mdpi.com/1660-3397/20/2/140 |
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