Evidence That pH-Titratable Groups Control the Activity of a Large Epithelial Chloride Channel

The effects of pH changes were examined on the properties of a large, voltage dependent, epithelial Cl^- channel from bovine tracheal cells. Alkaline solutions in the range pH = 7.4-9.2 had no detectable effects on channel conductance or gating. However, acid solutions significantly reduced channel open probability, raising the voltage required to open the channel. Analysis of channel activity in the acidic pH range suggested that at least one charged group on the channel with an apparent pK=6.09, is responsible for its voltage dependence. Neutralization of this charge does not eliminate the voltage dependence, but changes the energy difference between the closed and open states. The absence of any change in channel conductance over this wide pH range suggests that the protonation site is far removed from the channel permeation pathway.