Ruthenium red-mediated inhibition of large-conductance Ca2+-activated K+ channels in rat pituitary GH3 cells

Sheng-Nan Wu, Chung Ren Jan, Hui Fang Li

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19 Citations (Scopus)

Abstract

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 [I(K(Ca))] in a dose-dependent manner. The IC50 value of ruthenium red- induced inhibition of I(K(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 I(K(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 (BK(Ca)) channels. The ruthenium red-induced decrease in the channel activity of BK(Ca) channels was reversed by an increase in intracellular Ca2+ concentration. Ruthenium red also shifted the activation curve of BK(Ca) channels to positive membrane potentials. The change in the kinetic behavior of BK(Ca) 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 BK(Ca) channels in GH3 cells. This effect is independent on the inhibition of Ca2+ release from internal stores or mitochondria.

Original languageEnglish
Pages (from-to)998-1005
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume290
Issue number3
Publication statusPublished - 1999 Sep 1

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

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