Ammonium inhibition of Ca2+-dependent inwardly rectifying K+ currents in HeLa cells

The patch-clamp technique was used to examine the effect of ammonium on inwardly rectifying Ca2+-dependent K+ channels of HeLa cells. Ammonium added extracellularly blocked macroscopic K+ currents with an IC50 of 1.6 mM. Inhibition was fully reversible and voltage-independent and is not likely to be secondary to an increase in intracellular pH as this would have the opposite effect. In these experiments ammonium appeared to have an intracellular site of action. Intracellular ammonium rapidly and reversibly inhibits the activity of single Ca2+-dependent K+ channels underlying the macroscopic currents. This compound is often employed to manipulate intracellular pH but its use would not be indicated when full activity of the type of channels studied here needs to be unaltered.