The intriguing effect of ethanol and nicotine on
acetylcholine-sensitive potassium current IKAch: Insight from a
quantitative model

J 2019

The intriguing effect of ethanol and nicotine on acetylcholine-sensitive potassium current IKAch: Insight from a quantitative model

ŠIMURDA, Jiří, Milena ŠIMURDOVÁ a Markéta BÉBAROVÁ

Základní údaje

Originální název

The intriguing effect of ethanol and nicotine on acetylcholine-sensitive potassium current IKAch: Insight from a quantitative model

Autoři

ŠIMURDA, Jiří (203 Česká republika, domácí), Milena ŠIMURDOVÁ (203 Česká republika, domácí) a Markéta BÉBAROVÁ (203 Česká republika, garant, domácí)

Vydání

Plos One, SAN FRANCISCO, PUBLIC LIBRARY SCIENCE, 2019, 1932-6203

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30105 Physiology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 2.740

Kód RIV

RIV/00216224:14110/19:00108574

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.1371/journal.pone.0223448

UT WoS

000519247000001

Klíčová slova anglicky

ethanol; nicotine; acetylcholine-sensitive; IKAch; quantitative model

Štítky

14110515, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 5. 5. 2020 09:31, Mgr. Tereza Miškechová

Anotace

V originále

Recent experimental work has revealed unusual features of the effect of certain drugs on cardiac inwardly rectifying potassium currents, including the constitutively active and acetylcholine-induced components of acetylcholine-sensitive current (IKAch). These unusual features have included alternating susceptibility of the current components to activation and inhibition induced by ethanol or nicotine applied at various concentrations, and significant correlation between the drug effect and the current magnitude measured under drug-free conditions. To explain these complex drug effects, we have developed a new type of quantitative model to offer a possible interpretation of the effect of ethanol and nicotine on the IKAch channels. The model is based on a description of IKAch as a sum of particular currents related to the populations of channels formed by identical assemblies of different alpha-subunits. Assuming two different channel populations in agreement with the two reported functional IKAch-channels (GIRK1/4 and GIRK4), the model was able to simulate all the above-mentioned characteristic features of drug-channel interactions and also the dispersion of the current measured in different cells. The formulation of our model equations allows the model to be incorporated easily into the existing integrative models of electrical activity of cardiac cells involving quantitative description of IKAch. We suppose that the model could also help make sense of certain observations related to the channels that do not show inward rectification. This new ionic channel model, based on a concept we call population type, may allow for the interpretation of complex interactions of drugs with ionic channels of various types, which cannot be done using the ionic channel models available so far.

Návaznosti

MUNI/A/1255/2018, interní kód MU

Název: Kardiovaskulární systém a jeho regulace a dysregulace pod vlivem farmak (Akronym: KAREDYSFAR)

Investor: Masarykova univerzita, Kardiovaskulární systém a jeho regulace a dysregulace pod vlivem farmak, DO R. 2020_Kategorie A - Specifický výzkum - Studentské výzkumné projekty

NV16-30571A, projekt VaV

Název: Klinický význam a elektrofyziologické zhodnocení mutace c.926C>T genu KCNQ1 (p.T309I) jako možné „founder mutation“ syndromu dlouhého intervalu QT

Citovat

ŠIMURDA, Jiří, Milena ŠIMURDOVÁ a Markéta BÉBAROVÁ. The intriguing effect of ethanol and nicotine on acetylcholine-sensitive potassium current IKAch: Insight from a quantitative model. Plos One. SAN FRANCISCO: PUBLIC LIBRARY SCIENCE, 2019, roč. 14, č. 10, s. 1-19. ISSN 1932-6203. Dostupné z: https://dx.doi.org/10.1371/journal.pone.0223448.

@article{1606991,
   author = {Šimurda, Jiří and Šimurdová, Milena and Bébarová, Markéta},
   article_location = {SAN FRANCISCO},
   article_number = {10},
   doi = {http://dx.doi.org/10.1371/journal.pone.0223448},
   keywords = {ethanol; nicotine; acetylcholine-sensitive; IKAch; quantitative model},
   language = {eng},
   issn = {1932-6203},
   journal = {Plos One},
   title = {The intriguing effect of ethanol and nicotine on acetylcholine-sensitive potassium current IKAch: Insight from a quantitative model},
   url = {http://dx.doi.org/10.1371/journal.pone.0223448},
   volume = {14},
   year = {2019}
}

TY  - JOUR
ID  - 1606991
AU  - Šimurda, Jiří - Šimurdová, Milena - Bébarová, Markéta
PY  - 2019
TI  - The intriguing effect of ethanol and nicotine on acetylcholine-sensitive potassium current IKAch: Insight from a quantitative model
JF  - Plos One
VL  - 14
IS  - 10
SP  - 1-19
EP  - 1-19
PB  - PUBLIC LIBRARY SCIENCE
SN  - 19326203
KW  - ethanol
KW  - nicotine
KW  - acetylcholine-sensitive
KW  - IKAch
KW  - quantitative model
UR  - http://dx.doi.org/10.1371/journal.pone.0223448
L2  - http://dx.doi.org/10.1371/journal.pone.0223448
N2  - Recent experimental work has revealed unusual features of the effect of certain drugs on cardiac inwardly rectifying potassium currents, including the constitutively active and acetylcholine-induced components of acetylcholine-sensitive current (IKAch). These unusual features have included alternating susceptibility of the current components to activation and inhibition induced by ethanol or nicotine applied at various concentrations, and significant correlation between the drug effect and the current magnitude measured under drug-free conditions. To explain these complex drug effects, we have developed a new type of quantitative model to offer a possible interpretation of the effect of ethanol and nicotine on the IKAch channels. The model is based on a description of IKAch as a sum of particular currents related to the populations of channels formed by identical assemblies of different alpha-subunits. Assuming two different channel populations in agreement with the two reported functional IKAch-channels (GIRK1/4 and GIRK4), the model was able to simulate all the above-mentioned characteristic features of drug-channel interactions and also the dispersion of the current measured in different cells. The formulation of our model equations allows the model to be incorporated easily into the existing integrative models of electrical activity of cardiac cells involving quantitative description of IKAch. We suppose that the model could also help make sense of certain observations related to the channels that do not show inward rectification. This new ionic channel model, based on a concept we call population type, may allow for the interpretation of complex interactions of drugs with ionic channels of various types, which cannot be done using the ionic channel models available so far.
ER  -

ŠIMURDA, Jiří, Milena ŠIMURDOVÁ a Markéta BÉBAROVÁ. The intriguing effect of ethanol and nicotine on acetylcholine-sensitive potassium current IKAch: Insight from a quantitative model. \textit{Plos One}. SAN FRANCISCO: PUBLIC LIBRARY SCIENCE, 2019, roč.~14, č.~10, s.~1-19. ISSN~1932-6203. Dostupné z: https://dx.doi.org/10.1371/journal.pone.0223448.

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