Inward rectifying potassium currents resolved into components: modeling of complex drug actions
Language English Country Germany Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
16-30571A
Ministerstvo Zdravotnictví Ceské Republiky - International
PubMed
28948353
DOI
10.1007/s00424-017-2071-2
PII: 10.1007/s00424-017-2071-2
Knihovny.cz E-resources
- Keywords
- Cardiomyocytes, Dual effect, Ethanol, I K1, Inward rectifier potassium currents, Quantitative model,
- MeSH
- Action Potentials * MeSH
- Allosteric Regulation MeSH
- Potassium Channels, Inwardly Rectifying chemistry metabolism MeSH
- Ethanol pharmacology MeSH
- Myocytes, Cardiac drug effects metabolism physiology MeSH
- Rats MeSH
- Models, Cardiovascular MeSH
- Protein Multimerization MeSH
- Ventricular Function MeSH
- Heart Ventricles cytology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Potassium Channels, Inwardly Rectifying MeSH
- Ethanol MeSH
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.
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