Inhibition of the human intermediate-conductance, Ca2+-activated K+ channel by intracellular acidification

The effect of changes in pH on the gating properties of the cloned human intermediate-conductance, Ca2+-activated K+ channel (hIK) was studied using the patch-clamp technique. Multi-channel inside-out recordings of patches from HEK-293 cells stably expressing hIK channels revealed that the channel activity is modulated by changes in intracellular pH (pH(i)). Changes in extracellular pH (pH(o)) in the range from pH 6.0 to 8.2 did not affect the hIK whole-cell current. Intracellular acidification gradually decreased the activity of the hIK channel, approaching zero activity at pH(i) 6.0. Decreasing pH(i) altered neither the conductance nor the inward rectification of hIK channels. The proton-induced inhibition of the multichannel hIK patch current could not be counteracted by increasing the cytosolic Ca2+ concentration to 30 mu M. The molecular sensory mechanism underlying the proton-induced modulation of hIK gating is at present unknown.