Redox modulation of hslo Ca2+-activated K+ channels

The modulation of ion channel proteins by cellular redox potential has emerged recently as a significant determinant of channel function., We have investigated the influence oi sulfhydryl redox reagents on human brain Ca2+-activated K+ channels (halo) expressed in both human embryonic kidney 293 cells and Xenopus oocytes using macropatch and single-channel analysis, Intracellular application of the reducing agent dithiothreitol (DTT): (1) shifts the voltage of half-maximal channel activation (V-0.5) approximate to 18 mV to move negative potentials without affecting the maximal conductance or the slope of the voltage dependence; (2) slows by approximate to 10-fold a time-dependent right-shift in V-0.5, values ("run-down"); (3) speeds macroscopic current activation kinetics by approximate to 33%; and (4) increases the single-channel open probability without affecting the unitary conductance. In contrast to DTT treatment, oxidation with hydrogen peroxide shifts macropatch V-0.5 values to more positive potentials, increases the rate of channel run-down, and decreases the single-channel open probability. K-Ca channels cloned from Drosophila differ from hslo channels in that they show very little run-down and are not modulated by the addition of DTT. These data indicate that halo Ca2+-activated K+ channels may be modulated by changes in the cellular redox potential as well as by the transmembrane voltage and the cytoplasmic Ca2+ concentration.