The functional role of a bicuculline-sensitive Ca2+-activated K+ current in rat medial preoptic neurons.

Abstract

A Ca2+-activated K+ current was identified in neurons from the rat medial preoptic nucleus. Its functional role for the resting potential and for impulse generation was characterised by using the reversible blocking agent bicuculline methiodide. Acutely dissociated neurons were studied by perforated-patch recordings. The effect of bicuculline methiodide was investigated under voltage-clamp conditions to clearly identify the current affected. At membrane potentials > -50 mV, bicuculline methiodide rapidly (< 1 s) and reversibly blocked a steady outward current. Half-saturating concentration was 12 microM. The current amplitude increased with potential in the range -50 to 0 mV. The bicuculline-sensitive current was identified as an apamin-sensitive, Ca2+-dependent K+ current. It was neither affected by the GABAA receptor blocker picrotoxin (100 microM) nor by a changed pipette Cl- concentration, but was affected by substitution of extracellular K+ for Na+. The current was dependent on extracellular Ca2+ and was sensitive to 1 microM apamin but not to 200 nM charybdotoxin. A role for the Ca2+-dependent K+ current in setting the resting potential and controlling spontaneous firing frequency was observed under current-clamp conditions. Bicuculline methiodide (100 microM) induced a positive shift (5 +/- 1 mV; n = 18) of resting potential in all neurons tested. In the majority of spontaneously firing neurons, the firing frequency was reversibly affected, either increased or decreased depending on the cell, by bicuculline methiodide.