Differential inhibition of KCa2.3 and KCa2.2 channel macroscopic current by increasing [H+]o. (A) Representative outside-out macropatch KCa2.2 and KCa2.3 currents evoked by voltage ramps from −100 to +100 mV over 1 s in control conditions (pH 7.4) and in pH 6.6, 5.9, and 5.5. (B) Inhibition was voltage dependent, with less inhibition observed at depolarized levels. This was apparent when the fraction of unblocked current (KCa2.2, IpH5.9/IpH7.4; KCa2.3, IpH6.6/IpH7.4) was plotted against membrane voltage for KCa2.2 and KCa2.3 currents shown in A, indicating that block negative to 0 mV was voltage independent, and less inhibition was observed as the membrane potential approached +100 mV. (C) Concentration–inhibition relationships for the inhibition of KCa2.2 and KCa2.3 by [H+]o. Data points from different patches (n = 3–11) were fit with Eq. 1.