The role of the potassium inward rectifier in defining cell membrane potentials in low potassium media, analysed by computer simulation

Abstract A model is presented that describes the contributions of the potassium conductance and the Na + /K + pump to the steady state magnitude of the plasma membrane potential, V rest , at different concentrations of potassium in the extracellular fluid: K o . The particular properties of the potassium inward rectifier, IKR, are shown to explain that V rest frequently depolarises on lowering K o below a critical value, because the IKR is only conductive when V m is near to the potassium equilibrium potential or more negative. The model aims at a generic description of the process based on compartmental analysis. It is worked out to describe V rest in mouse muscle fibres. Sensitivity analysis demonstrates that the process of switching off the IKR depends critically on the margin between V rest and E K , allowed for the IKR to remain open and the power of the Na/K pump to keep this margin small during the reduction of K o . However, cells exposed to K o just higher than the critical value may eventually also depolarize due to excessive loss of potassium. The model also demonstrates that loss of potassium membrane selectivity after blocking the Na/K pump by ouabain requires a mechanism additional to the above mentioned properties of the inward rectifier.