BICUCULLINE METHIODIDE POTENTIATES NMDA-DEPENDENT BURST FIRING IN RATDOPAMINE NEURONS BY BLOCKING APAMIN-SENSITIVE CA2-ACTIVATED K+ CURRENTS()

Apamin, a bee venom toxin which blocks a Ca2+-dependent K+ current, po tentiates N-methyl-D-aspartate (NMDA)-induced burst firing in dopamine neurons. We now report that burst firing is also potentiated by an ap amin-like effect of bicuculline methiodide (BMI) at the same concentra tion (30 mu M) which blocks GABA(A) receptors in vitro. Using microele ctrodes to record intracellularly from rat dopamine neurons in the mid brain slice, BMI reduced the apamin-sensitive afterhyperpolarization i n all cells tested. BMI also mimicked apamin (100 nM) by potentiating burst firing produced by a concentration of NMDA (10 mu M) which is to o low to evoke burst firing when perfused alone. When recording under voltage-clamp, both BMI and apamin reduced a depolarization-activated outward current which was also sensitive to perfusate containing no-ad ded Ca2+. Although picrotoxin (100 mu M) and bicuculline free base (30 mu M) blocked the inhibition of firing produced by the GABA(A) agonis t isoguvacine (100 mu M), neither had apamin-like effects. We conclude that BMI potentiates burst firing by blocking an apamin-sensitive Ca2 +-activated K+ current. (C) 1997 Elsevier Science Ireland Ltd.