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Mechanistic insight...
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Bohannon, Briana M.Univ Miami, FL 33136 USA
(författare)
Mechanistic insights into robust cardiac I-Ks potassium channel activation by aromatic polyunsaturated fatty acid analogues
- Artikel/kapitelEngelska2023
Förlag, utgivningsår, omfång ...
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eLIFE SCIENCES PUBL LTD,2023
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electronicrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:liu-196777
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-196777URI
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https://doi.org/10.7554/eLife.85773DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
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Funding Agencies|HORIZON EUROPE European Research Council; Swedish Research Council; National Institutes of Health [2021-01885]; [R01HL131461]; [850622]
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Voltage-gated potassium (K-V) channels are important regulators of cellular excitability and control action potential repolarization in the heart and brain. K-V channel mutations lead to disordered cellular excitability. Loss-of-function mutations, for example, result in membrane hyperexcitability, a characteristic of epilepsy and cardiac arrhythmias. Interventions intended to restore K-V channel function have strong therapeutic potential in such disorders. Polyunsaturated fatty acids (PUFAs) and PUFA analogues comprise a class of K-V channel activators with potential applications in the treatment of arrhythmogenic disorders such as long QT syndrome (LQTS). LQTS is caused by a loss-of-function of the cardiac I-Ks channel - a tetrameric potassium channel complex formed by K(V)7.1 and associated KCNE1 protein subunits. We have discovered a set of aromatic PUFA analogues that produce robust activation of the cardiac I-Ks channel, and a unique feature of these PUFA analogues is an aromatic, tyrosine head group. We determine the mechanisms through which tyrosine PUFA analogues exert strong activating effects on the I-Ks channel by generating modified aromatic head groups designed to probe cation-pi interactions, hydrogen bonding, and ionic interactions. We found that tyrosine PUFA analogues do not activate the I-Ks channel through cation-pi interactions, but instead do so through a combination of hydrogen bonding and ionic interactions.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Jowais, Jessica J.Univ Miami, FL 33136 USA
(författare)
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Nyberg, LeifLinköpings universitet,Institutionen för biomedicinska och kliniska vetenskaper,Medicinska fakulteten,Univ Miami, FL 33136 USA(Swepub:liu)n/a
(författare)
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Olivier-Meo, VanessaUniv Miami, FL 33136 USA
(författare)
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Corradi, ValentinaUniv Calgary, Canada
(författare)
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Tieleman, D. PeterUniv Calgary, Canada
(författare)
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Liin, SaraLinköpings universitet,Avdelningen för neurobiologi,Medicinska fakulteten(Swepub:liu)sarbo42
(författare)
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Larsson, H. PeterUniv Miami, FL 33136 USA
(författare)
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Univ Miami, FL 33136 USAInstitutionen för biomedicinska och kliniska vetenskaper
(creator_code:org_t)
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Ingår i:eLIFE: eLIFE SCIENCES PUBL LTD122050-084X
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