Gain of function of Kir4.1 channel increases cell resistance to changes of potassium fluxes and cell volume evoked by ammonia and hypoosmotic stress

The Kir4.1 channel is an inward rectifying potassium channel involved in the control of potassium and water movement in mammalian cells. To evaluate independently the role of Kir4.1 alone and without interaction with other cellular effectors, we compared 86Rb fluxes and cell volume in Kir4.1 transfected cells (Kir4.1+) with cells transfected with an empty vector (Kir4.1-). Transfection with Kir4.1 neither increased 86Rb uptake nor 86Rb efflux from cells in isotonic medium. Pretreatment with ammonia (5 mM ammonium chloride) in isotonic medium produced a pronounced increase of 86Rb uptake and a moderate decrease of cell volume in Kir4.1- but not in Kir4.1+ cells. However, pretreatment evoked no change in 86Rb efflux in either cell type. Hypotonic treatment (HT) markedly increased 86Rb efflux in Kir4.1- cells and increased cell volume in both cell types. Although pretreatment with ammonia did not alter the effect of HT on 86Rb efflux in either Kir4.1+ or Kir4.1- cells, it potentiated the effect of hypotonic treatment in increasing cell volume in Kir4.1- cells. The results demonstrate that the presence of Kir4.1 in cells increases their resistance to alterations of potassium fluxes and/or cell volume imposed by ammonia and hypotonicity.