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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F18%3A00106922" target="_blank" >RIV/00216224:14110/18:00106922 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1007/s00424-017-2071-2" target="_blank" >http://dx.doi.org/10.1007/s00424-017-2071-2</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00424-017-2071-2" target="_blank" >10.1007/s00424-017-2071-2</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30105 - Physiology (including cytology)

Projekt

<a href="/cs/project/NV16-30571A" target="_blank" >NV16-30571A: Klinický význam a elektrofyziologické zhodnocení mutace c.926C>T genu KCNQ1 (p.T309I) jako možné „founder mutation“ syndromu dlouhého intervalu QT</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY

ISSN

0031-6768

e-ISSN

1432-2013

Svazek periodika

470

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

11

Strana od-do

315-325

Kód UT WoS článku

000423161400010

EID výsledku v databázi Scopus

2-s2.0-85029798851