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.
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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
Original language English
Type of outcome Article in a journal
Field of Study 30105 Physiology
Country of publisher United States of America
Confidentiality degree is not subject to a state or trade secret
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
Tags 14110515, EL OK, rivok
Tags International impact, Reviewed
Changed by Changed by: Soňa Böhmová, učo 232884. Changed: 10/2/2019 15:04.
Abstract
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 projectName: Klinický význam a elektrofyziologické zhodnocení mutace c.926C>T genu KCNQ1 (p.T309I) jako možné „founder mutation“ syndromu dlouhého intervalu QT
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