Owing to their relatively slow kinetics in acting on the external potassium concentration ([K⁺]_e) kidneys control [K⁺]_e only indirectly by changing the total body potassium content (TBP). At a given TBP [K⁺]_e is determined by the so called internal potassium balance on which skeletal muscle has a major impact. So far it has not been investigated in detail how ion channels and transporters of muscle fibers affect [K⁺]_e. We studied the influence of some important channels on [K⁺]_e by a computer simulation which accounts for a variable extracellular space. Increasing the resting sodium conductance raises [K⁺]_e as it is seen in familial hyperkalemic periodic paralysis, a disease with a gain-of-function mutation in skeletal muscle's voltage-gated sodium channel. This is caused by cell depolarisation. Reducing the resting conductance of inward rectifier potassium channels (Kir) accumulates potassium inside cells finally leading to a depolarised state of muscle with a drastically reduced [K⁺]_e. This represents the hypokalemic paralysis of Andersen-Tawil-Syndrome in which a mutation of the Kir 2.1 is the underlying cause of the disease. Incorporating a volume-sensitive Na⁺/K⁺/2 Cl^--cotransporter into the model allows us to simulate shifts of potassium as they are caused by hypo- and hyperosmolality.

With this computer model we are able to predict how channels and transporters influence the distribution of ions across the cell membrane.