Redox modulation of large conductance calcium-activated potassium channels in CA1 pyramidal neurons from adult rat hippocampus

Redox regulation of BKCa channels was studied in CA1 pyramidal neurons of adult rat hippocampus by using inside-out configuration of patch clamp. Intracellular application of oxidizing agent 5,5'-dithio-bis(2-nitrobenzoic acid) (DTNB) markedly increased activity of BKCa channels and this stimulating action persisted even after washout. In contrast, the reducing agent dithiothreitol (DTT) had no apparent effects on channel activity but could reverse the pre-exposure of DTNB-induced enhancement. The increase in channel activity produced by DTNB was due to shortened closed time as well as prolonged open time. The effects exerted by another redox couple glutathione disulphide and its reducing form were similar as DTNB and DTT. The present results indicate that BKCa channels in CA1 pyramidal neurons can be modulated by intracellular redox potential, and that augmentation of BKCa channels by oxidative stress might contribute to the postischemic electrophysiological alterations of CA1 pyramidal neurons. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.