Bicuculline free base blocks voltage-activated K+ currents in rat medial preoptic neurons

The effects of the well-known GABA(A)-receptor blocker bicuculline on voltage-gated K+ currents were studied in neurons from the medial preoptic nucleus (MPN) of rat. Whole-cell currents were recorded using the perforated-patch technique. Voltage steps from -54 to +6 mV resulted in tetraethylammonium-sensitive K+ currents of delayed rectifier type. The total K+ current (at 300 ms), including Ca2+-dependent and Ca2+-independent components, was reversibly reduced (17 +/- 4%) by 100 muM bicuculline methiodide and (37 +/- 5%) by 100 muM bicuculline as free base. The Ca2+ -independent fraction (77 +/- 2%) of K+ current evoked by a voltage step was. however, reduced (54 +/- 6%) only by bicuculline free base, but was not affected by bicuculline methiodide. The half-saturating concentration of bicuculline free base for blocking this purely voltage-gated K+ current was 113 muM, whereas for blocking a steady Ca2+-dependent K+ current it was 36 muM. The bicuculline-sensitive voltage-gated K+ current was composed of 4-AP-sensitive and 4-AP-resistant components with different kinetic properties. No component of the purely voltage-gated K+ current was affected neither by 100 nM alpha-dendrotoxin nor by 100 nM I-dendrotoxin. The possible K+-channel subtypes mediating the bicuculline-sensitive Current in MPN neurons are discussed. (C) 2003 Elsevier Ltd. All rights reserved.