Pflügers Archiv - European Journal of Physiology

, Volume 470, Issue 2, pp 315–325 | Cite as

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

  • Jiří Šimurda
  • Milena Šimurdová
  • Markéta BébarováEmail author
Ion channels, receptors and transporters
Part of the following topical collections:
  1. Ion channels, receptors and transporters


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.


Quantitative model Cardiomyocytes Inward rectifier potassium currents IK1 Ethanol Dual effect 



Drug concentration


Fraction of j th channel population


Fraction of channels showing activation

f2, f3

Fractions of channels showing inhibition


Total conductance of I Kir,x channel

GKir,x,j, Gj

Conductance of the jth channel population


Steady-state conductance of the jth channel population

G0,jG1,j, G2,j

Steady-state conductance of the jth channel population related to sets of vacant channels, channels occupied by one or two drug molecules, respectively

IKir, IKir,x

Inward rectifier potassium current (generally)

IKir,x,j, Ij

Current through jth channel population


Inward rectifier potassium currents


I K1 through jth channel population

INa, ICa, Ito

Sodium, calcium, and transient outward potassium currents


Individual populations of identical channels (j = 1,…,n)


Extracellular concentration of potassium ions


Molecular identities of I K1 channels (Kir2.1, Kir2.2, Kir2.3)


Molecular identities of I KAch channels (Kir3.1, Kir3.4)


Molecular identities of I KATP channels

K1,j, K2,j

Binding constants (binding of the first and the second molecule, respectively)


Number of different populations


Phospholipid phosphatidylinositol-4,5-bisphosphate


Time constants related to jth channel population


Membrane voltage


Equilibrium voltage of potassium ions

x0,j, x1,j, x2,j

Probability of channels (pertaining to jth channel population) to be found drug free, occupied by one, or by two drug molecules, respectively



The authors wish to thank Prof. P. Bravený for reading the manuscript and valuable comments.


This study was supported by Ministry of Health of the Czech Republic, grant nr. 16-30571A.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Department of Physiology, Faculty of MedicineMasaryk UniversityBrnoCzech Republic

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