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Mar Drugs
2022 Feb 15;202:. doi: 10.3390/md20020140.
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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 EL
,
Béress L
,
Gladkikh I
,
Leychenko E
,
Undheim EAB
,
Peigneur S
,
Tytgat J
.
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(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.
201907060021 China Scholarship Council, GOA4919N FWO-Vlaanderen, GOE7120N FWO-Vlaanderen, GOC2319N FWO-Vlaanderen, 12W7822N FWO-Vlaanderen, 2016/04761-4 São Paulo Research Foundation, 88881.186830/2018-01 Coordenação de Aperfeicoamento de Pessoal de Nível Superior
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