Isopimaric acid - a multi-targeting ion channel modulator reducing excitability and arrhythmicity in a spontaneously beating mouse atrial cell line

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Salari, Sajjad,1978-Linköpings universitet,Medicinska fakulteten,Avdelningen för cellbiologi (author)

Isopimaric acid - a multi-targeting ion channel modulator reducing excitability and arrhythmicity in a spontaneously beating mouse atrial cell line

Article/chapterEnglish2018

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2017-06-09
Wiley-VCH Verlagsgesellschaft,2018
electronicrdacarrier

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LIBRIS-ID:oai:DiVA.org:liu-144564
https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-144564URI
https://doi.org/10.1111/apha.12895DOI

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Language:English
Summary in:English

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

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Funding Agencies|Swedish Research Council; Swedish Heart-Lung Foundation; Swedish Brain Foundation; ALF
AimAtrial fibrillation is the most common persistent cardiac arrhythmia, and it is not well controlled by present drugs. Because some resin acids open voltage-gated potassium channels and reduce neuronal excitability, we explored the effects of the resin acid isopimaric acid (IPA) on action potentials and ion currents in cardiomyocytes. MethodsSpontaneously beating mouse atrial HL-1 cells were investigated with the whole-cell patch-clamp technique. Results1-25 mol L-1 IPA reduced the action potential frequency by up to 50%. The effect of IPA on six different voltage-gated ion channels was investigated; most voltage-dependent parameters of ion channel gating were shifted in the negative direction along the voltage axis, consistent with a hypothesis that a lipophilic and negatively charged compound binds to the lipid membrane close to the positively charged voltage sensor of the ion channels. The major finding was that IPA inactivated sodium channels and L- and T-type calcium channels and activated the rapidly activating potassium channel and the transient outward potassium channel. Computer simulations of IPA effects on all of the ion currents were consistent with a reduced excitability, and they also showed that effects on the Na channel played the largest role to reduce the action potential frequency. Finally, induced arrhythmia in the HL-1 cells was reversed by IPA. ConclusionLow concentrations of IPA reduced the action potential frequency and restored regular firing by altering the voltage dependencies of several voltage-gated ion channels. These findings can form the basis for a new pharmacological strategy to treat atrial fibrillation.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Cell- och molekylärbiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Cell and Molecular Biology hsv//eng
arrhythmia; atrial fibrillation; ion channels; isopimaric acid; patch clamp; resin acid

Added entries (persons, corporate bodies, meetings, titles ...)

Silverå Ejneby, Malin,1987-Linköpings universitet,Avdelning för neurobiologi,Medicinska fakulteten(Swepub:liu)malsi14 (author)
Brask, Johan,1971-Linköpings universitet,Avdelning för neurobiologi,Medicinska fakulteten(Swepub:liu)johbr00 (author)
Elinder, Fredrik,1966-Linköpings universitet,Avdelning för neurobiologi,Medicinska fakulteten(Swepub:liu)freel71 (author)
Linköpings universitetMedicinska fakulteten (creator_code:org_t)

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In:Acta Physiologica: Wiley-VCH Verlagsgesellschaft222:11748-17081748-1716

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