TY - JOUR T1 - Ruthenium Red-Mediated Inhibition of Large-Conductance Ca<sup>2+</sup>-Activated K<sup>+</sup> Channels in Rat Pituitary GH<sub>3</sub> Cells JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 998 LP - 1005 VL - 290 IS - 3 AU - Sheng-Nan Wu AU - Chung-Ren Jan AU - Hui-Fang Li Y1 - 1999/09/01 UR - http://jpet.aspetjournals.org/content/290/3/998.abstract N2 - The ionic mechanism of actions of ruthenium red was examined in rat anterior pituitary GH3 cells. In whole-cell recording experiments, ruthenium red reversibly caused an inhibition of Ca2+-activated K+ current [IK(Ca)] in a dose-dependent manner. The IC50value of ruthenium red-induced inhibition of IK(Ca) was 15 μM. Neither carbonyl cyanide m-chlorophenyl hydrazone (CCCP; 10 μM), an uncoupler of oxidative phosphorylation in mitochondria, nor cyclosporin A (200 nM), an inhibitor of the mitochondrial permeability transition pore, affected the amplitude of IK(Ca). In inside-out configuration, application of ruthenium red (50 μM) into the bath medium did not change single-channel conductance but significantly suppressed the activity of large-conductance Ca2+-activated K+ channel (BKCa) channels. The ruthenium red-induced decrease in the channel activity of BKCa channels was reversed by an increase in intracellular Ca2+ concentration. Ruthenium red also shifted the activation curve of BKCa channels to positive membrane potentials. The change in the kinetic behavior of BKCa channels caused by ruthenium red in these cells is due to a decrease in mean open time and an increase in mean closed time. Ruthenium red (50 μM) did not affect the amplitude of voltage-dependent K+ current but produced a significant reduction of voltage-dependent L-type Ca2+ current. These results indicate that ruthenium red can directly suppress the activity of BKCa channels in GH3 cells. This effect is independent on the inhibition of Ca2+ release from internal stores or mitochondria. The American Society for Pharmacology and Experimental Therapeutics ER -