liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Biaryl sulfonamide motifs up- or down-regulate ion channel activity by activating voltage sensors
Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.ORCID iD: 0000-0001-8493-0114
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.ORCID iD: 0000-0003-3852-1015
Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
Show others and affiliations
2018 (English)In: The Journal of General Physiology, ISSN 0022-1295, E-ISSN 1540-7748, Vol. 150, no 8, p. 1215-1230Article in journal (Refereed) Published
Abstract [en]

Voltage-gated ion channels are key molecules for the generation of cellular electrical excitability. Many pharmaceutical drugs target these channels by blocking their ion-conducting pore, but in many cases, channel-opening compounds would be more beneficial. Here, to search for new channel-opening compounds, we screen 18,000 compounds with high-throughput patch-clamp technology and find several potassium-channel openers that share a distinct biaryl-sulfonamide motif. Our data suggest that the negatively charged variants of these compounds bind to the top of the voltage-sensor domain, between transmembrane segments 3 and 4, to open the channel. Although we show here that biaryl-sulfonamide compounds open a potassium channel, they have also been reported to block sodium and calcium channels. However, because they inactivate voltage-gated sodium channels by promoting activation of one voltage sensor, we suggest that, despite different effects on the channel gates, the biaryl-sulfonamide motif is a general ion-channel activator motif. Because these compounds block action potential-generating sodium and calcium channels and open an action potential-dampening potassium channel, they should have a high propensity to reduce excitability. This opens up the possibility to build new excitability-reducing pharmaceutical drugs from the biaryl-sulfonamide scaffold.

Place, publisher, year, edition, pages
ROCKEFELLER UNIV PRESS , 2018. Vol. 150, no 8, p. 1215-1230
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:liu:diva-150493DOI: 10.1085/jgp.201711942ISI: 000440815100015PubMedID: 30002162OAI: oai:DiVA.org:liu-150493DiVA, id: diva2:1241694
Note

Funding Agencies|Swedish Research Council [2016-02615]; Swedish Heart-Lung Foundation [20150672]; Swedish Brain Foundation [2016-0326]; Swedish Society for Medical Research

Available from: 2018-08-24 Created: 2018-08-24 Last updated: 2018-09-10

Open Access in DiVA

fulltext(3430 kB)82 downloads
File information
File name FULLTEXT01.pdfFile size 3430 kBChecksum SHA-512
8deb081a85e0707fe0471c6e420927928e73d551ddcd67b5f8ca600c91360a8f54907f77ca765d43d90cae1f014b2c26a4b1e8457b3e6387ad7fe86d4c477ac9
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Liin, SaraLund, Per-EricLarsson, JohanBrask, JohanWallner, BjörnElinder, Fredrik
By organisation
Divison of NeurobiologyFaculty of Medicine and Health SciencesDivision of Cell BiologyBioinformaticsFaculty of Science & Engineering
In the same journal
The Journal of General Physiology
Pharmacology and Toxicology

Search outside of DiVA

GoogleGoogle Scholar
Total: 82 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 143 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf