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

Abstract

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 Ca 2+-dependent and Ca 2+-independent components, was reversibly reduced (17 ± 4%) by 100 μM bicuculline methiodide and (37 ± 5%) by 100 μM bicuculline as free base. The Ca 2+-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 μM, whereas for blocking a steady Ca 2+-dependent K + current it was 36 μM. 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 α-dendrotoxin nor by 100 nM I-dendrotoxin. The possible K +-channel subtypes mediating the bicuculline-sensitive current in MPN neurons are discussed.