Modulation of large conductance calcium-activated potassium channels from rat hippocampal neurons by glutathione

We have investigated the modulation of neuronal large conductance Ca2+-activated K+ channels by glutathione. Single channel recordings were made from cultured neonatal rat hippocampal neurons by using excised inside-out patch clamp method. Glutathione, a physiological sulfhydryl specific reducing reagent, increased channel activities in concentration dependent manner with half activation concentration of 710 microM. Conversely, oxidized form of glutathione inhibited channel activities with half inhibition concentration of 520 microM. Our results provide direct evidence that when neuronal large conductance Ca2+-activated K+ channels are exposed to reducing or oxidizing environments, channel activities are increased or decreased in opposite directions due to the redox modification. This may constitute an important regulatory mechanism of neuronal Ca2+-activated K+ channel activities.