Inward rectifying potassium currents resolved into components:
modeling of complex drug actions

J 2018

Inward rectifying potassium currents resolved into components: modeling of complex drug actions

ŠIMURDA, Jiří, Milena ŠIMURDOVÁ and Markéta BÉBAROVÁ

Basic information

Original name

Inward rectifying potassium currents resolved into components: modeling of complex drug actions

Authors

ŠIMURDA, Jiří (203 Czech Republic, belonging to the institution), Milena ŠIMURDOVÁ (203 Czech Republic, belonging to the institution) and Markéta BÉBAROVÁ (203 Czech Republic, guarantor, belonging to the institution)

Edition

PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, NEW YORK, SPRINGER, 2018, 0031-6768

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30105 Physiology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 3.377

RIV identification code

RIV/00216224:14110/18:00106922

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1007/s00424-017-2071-2

UT WoS

000423161400010

Keywords in English

Quantitative model; Cardiomyocytes; Inward rectifier potassium currents; I-K1; Ethanol; Dual effect

Abstract

V originále

Inward rectifier potassium currents (I (Kir,x)) belong to prominent ionic currents affecting both resting membrane voltage and action potential repolarization in cardiomyocytes. In existing integrative models of electrical activity of cardiac cells, they have been described as single current components. The proposed quantitative model complies with findings indicating that these channels are formed by various homomeric or heteromeric assemblies of channel subunits with specific functional properties. Each I (Kir,x) may be expressed as a total of independent currents via individual populations of identical channels, i.e., channels formed by the same combination of their subunits. Solution of the model equations simulated well recently observed unique manifestations of dual ethanol effect in rat ventricular and atrial cells. The model reflects reported occurrence of at least two binding sites for ethanol within I (Kir,x) channels related to slow allosteric conformation changes governing channel conductance and inducing current activation or inhibition. Our new model may considerably improve the existing models of cardiac cells by including the model equations proposed here in the particular case of the voltage-independent drug-channel interaction. Such improved integrative models may provide more precise and, thus, more physiologically relevant results.

Links

NV16-30571A, research and development project

Name: 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 and Markéta BÉBAROVÁ. Inward rectifying potassium currents resolved into components: modeling of complex drug actions. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY. NEW YORK: SPRINGER, 2018, vol. 470, No 2, p. 315-325. ISSN 0031-6768. Available from: https://dx.doi.org/10.1007/s00424-017-2071-2.

@article{1418464,
   author = {Šimurda, Jiří and Šimurdová, Milena and Bébarová, Markéta},
   article_location = {NEW YORK},
   article_number = {2},
   doi = {http://dx.doi.org/10.1007/s00424-017-2071-2},
   keywords = {Quantitative model; Cardiomyocytes; Inward rectifier potassium currents; I-K1; Ethanol; Dual effect},
   language = {eng},
   issn = {0031-6768},
   journal = {PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY},
   title = {Inward rectifying potassium currents resolved into components: modeling of complex drug actions},
   volume = {470},
   year = {2018}
}

TY  - JOUR
ID  - 1418464
AU  - Šimurda, Jiří - Šimurdová, Milena - Bébarová, Markéta
PY  - 2018
TI  - Inward rectifying potassium currents resolved into components: modeling of complex drug actions
JF  - PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
VL  - 470
IS  - 2
SP  - 315-325
EP  - 315-325
PB  - SPRINGER
SN  - 00316768
KW  - Quantitative model
KW  - Cardiomyocytes
KW  - Inward rectifier potassium currents
KW  - I-K1
KW  - Ethanol
KW  - Dual effect
N2  - Inward rectifier potassium currents (I (Kir,x)) belong to prominent ionic currents affecting both resting membrane voltage and action potential repolarization in cardiomyocytes. In existing integrative models of electrical activity of cardiac cells, they have been described as single current components. The proposed quantitative model complies with findings indicating that these channels are formed by various homomeric or heteromeric assemblies of channel subunits with specific functional properties. Each I (Kir,x) may be expressed as a total of independent currents via individual populations of identical channels, i.e., channels formed by the same combination of their subunits. Solution of the model equations simulated well recently observed unique manifestations of dual ethanol effect in rat ventricular and atrial cells. The model reflects reported occurrence of at least two binding sites for ethanol within I (Kir,x) channels related to slow allosteric conformation changes governing channel conductance and inducing current activation or inhibition. Our new model may considerably improve the existing models of cardiac cells by including the model equations proposed here in the particular case of the voltage-independent drug-channel interaction. Such improved integrative models may provide more precise and, thus, more physiologically relevant results.
ER  -

ŠIMURDA, Jiří, Milena ŠIMURDOVÁ and Markéta BÉBAROVÁ. Inward rectifying potassium currents resolved into components: modeling of complex drug actions. \textit{PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY}. NEW YORK: SPRINGER, 2018, vol.~470, No~2, p.~315-325. ISSN~0031-6768. Available from: https://dx.doi.org/10.1007/s00424-017-2071-2.

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