Please use this identifier to cite or link to this item: http://hdl.handle.net/10995/101402
Title: Gap19, a Cx43 hemichannel inhibitor, acts as a gating modifier that decreases main state opening while increasing substate gating
Authors: Lissoni, A.
Wang, N.
Nezlobinskii, T.
De Smet, M.
Panfilov, A. V.
Vandersickel, N.
Leybaert, L.
Witschas, K.
Issue Date: 2020
Publisher: MDPI AG
Citation: Gap19, a Cx43 hemichannel inhibitor, acts as a gating modifier that decreases main state opening while increasing substate gating / A. Lissoni, N. Wang, T. Nezlobinskii, et al. — DOI 10.3390/ijms21197340 // International Journal of Molecular Sciences. — 2020. — Vol. 21. — Iss. 19. — P. 1-15. — 7340.
Abstract: Cx43 hemichannels (HCs) are electrically and chemically gated transmembrane pores with low open probability and multiple conductance states, which makes kinetic studies of channel gating in large datasets challenging. Here, we developed open access software, named HemiGUI, to analyze HC gating transitions and investigated voltage-induced HC opening based on up to ≈4000 events recorded in HeLa-Cx43-overexpressing cells. We performed a detailed characterization of Cx43 HC gating profiles and specifically focused on the role of the C-terminal tail (CT) domain by recording the impact of adding an EGFP tag to the Cx43 CT end (Cx43-EGFP) or by supplying the Cx43 HC-inhibiting peptide Gap19 that interferes with CT interaction with the cytoplasmic loop (CL). We found that Gap19 not only decreased HC opening activity to the open state (≈217 pS) but also increased the propensity of subconductance (≈80 pS) transitions that additionally became slower as compared to the control. The work demonstrates that large sample transition analysis allows detailed investigations on Cx43 HC gating and shows that Gap19 acts as a HC gating modifier by interacting with the CT that forms a crucial gating element. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Keywords: AUTOMATED ANALYSIS
CHANNEL GATING
GRAPHIC USER INTERFACE
TRANSITION ANALYSIS
CONNEXIN 43
ENHANCED GREEN FLUORESCENT PROTEIN
GAP JUNCTION PROTEIN
GAP19 PROTEIN
UNCLASSIFIED DRUG
CONNEXIN 43
GJA1 PROTEIN, HUMAN
GREEN FLUORESCENT PROTEIN
PEPTIDE
ARTICLE
CARBOXY TERMINAL SEQUENCE
CHANNEL GATING
CONTROLLED STUDY
CYTOPLASM
HELA CELL LINE
HUMAN
HUMAN CELL
PROTEIN DOMAIN
PROTEIN EXPRESSION
PROTEIN PROTEIN INTERACTION
CHANNEL GATING
CHEMISTRY
GAP JUNCTION
GENETICS
KINETICS
SOFTWARE
CONNEXIN 43
GAP JUNCTIONS
GREEN FLUORESCENT PROTEINS
HELA CELLS
HUMANS
ION CHANNEL GATING
KINETICS
PEPTIDES
SOFTWARE
URI: http://hdl.handle.net/10995/101402
Access: info:eu-repo/semantics/openAccess
SCOPUS ID: 85092199944
PURE ID: 14157736
15246d95-43e6-4942-b9a9-896e34d53a43
ISSN: 16616596
DOI: 10.3390/ijms21197340
metadata.dc.description.sponsorship: This work was supported by the Fund for Scientific Research Flanders, Belgium (G052718N to L. Leybaert) and Ghent University (BOF 01IO8314 to A. Lissoni). A. V. Panfilov was supported by a grant from the Ministry of Science and Higher Education of the Russian Federation (agreement 075-15-2020-800). M. De Smet was supported by a personal grant from the Research Foundation Flanders (1124418N). N. Wang was supported by Belspo – IAP: P7/10.
Appears in Collections:Научные публикации, проиндексированные в SCOPUS и WoS CC

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