Fatty acid analogue N-arachidonoyl taurine restores function of IKs channels with diverse long QT mutations
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Fatty acid analogue N-arachidonoyl taurine restores function of IKs channels with diverse long QT mutations. / Liin, Sara I; Larsson, Johan E; Barro-Soria, Rene; Bentzen, Bo Hjorth; Larsson, H Peter.
I: eLife, Bind 5, e20272, 30.09.2016.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Fatty acid analogue N-arachidonoyl taurine restores function of IKs channels with diverse long QT mutations
AU - Liin, Sara I
AU - Larsson, Johan E
AU - Barro-Soria, Rene
AU - Bentzen, Bo Hjorth
AU - Larsson, H Peter
PY - 2016/9/30
Y1 - 2016/9/30
N2 - About 300 loss-of-function mutations in the IKs channel have been identified in patients with Long QT syndrome and cardiac arrhythmia. How specific mutations cause arrhythmia is largely unknown and there are no approved IKs channel activators for treatment of these arrhythmias. We find that several Long QT syndrome-associated IKs channel mutations shift channel voltage dependence and accelerate channel closing. Voltage-clamp fluorometry experiments and kinetic modeling suggest that similar mutation-induced alterations in IKs channel currents may be caused by different molecular mechanisms. Finally, we find that the fatty acid analogue N-arachidonoyl taurine restores channel gating of many different mutant channels, even though the mutations are in different domains of the IKs channel and affect the channel by different molecular mechanisms. N-arachidonoyl taurine is therefore an interesting prototype compound that may inspire development of future IKs channel activators to treat Long QT syndrome caused by diverse IKs channel mutations.
AB - About 300 loss-of-function mutations in the IKs channel have been identified in patients with Long QT syndrome and cardiac arrhythmia. How specific mutations cause arrhythmia is largely unknown and there are no approved IKs channel activators for treatment of these arrhythmias. We find that several Long QT syndrome-associated IKs channel mutations shift channel voltage dependence and accelerate channel closing. Voltage-clamp fluorometry experiments and kinetic modeling suggest that similar mutation-induced alterations in IKs channel currents may be caused by different molecular mechanisms. Finally, we find that the fatty acid analogue N-arachidonoyl taurine restores channel gating of many different mutant channels, even though the mutations are in different domains of the IKs channel and affect the channel by different molecular mechanisms. N-arachidonoyl taurine is therefore an interesting prototype compound that may inspire development of future IKs channel activators to treat Long QT syndrome caused by diverse IKs channel mutations.
U2 - 10.7554/eLife.20272
DO - 10.7554/eLife.20272
M3 - Journal article
C2 - 27690226
VL - 5
JO - eLife
JF - eLife
SN - 2050-084X
M1 - e20272
ER -
ID: 173130697