Bicuculline methiodide potentiates NMDA-dependent burst firing in rat dopamine neurons by blocking apamin-sensitive Ca2+-activated K+ currents.
Apamin, a bee venom toxin which blocks a Ca2+-dependent K+ current, potentiates N-methyl-D-aspartate (NMDA)-induced burst firing in dopamine neurons. We now report that burst firing is also potentiated by an apamin-like effect of bicuculline methiodide (BMI) at the same concentration (30 microM) which blocks GABA(A) receptors in vitro. Using microelectrodes to record intracellularly from rat dopamine neurons in the midbrain slice, BMI reduced the apamin-sensitive afterhyperpolarization in all cells tested. BMI also mimicked apamin (100 nM) by potentiating burst firing produced by a concentration of NMDA (10 microM) which is too 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-added Ca2+. Although picrotoxin (100 microM) and bicuculline free base (30 microM) blocked the inhibition of firing produced by the GABA(A) agonist isoguvacine (100 microM), neither had apamin-like effects. We conclude that BMI potentiates burst firing by blocking an apamin-sensitive Ca2+-activated K+ current.
Johnson
S W
SW
Department of Physiology and Pharmacology, Oregon Health Sciences University, Portland 97201, USA. johnsost@ohsu.edu
Seutin
V
V
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001640:Bicuculline / Q000031:analogs & derivatives* / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology; D004357:Drug Synergism; D004594:Electrophysiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D010507:Periodicity; D010852:Picrotoxin / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D017557:Ventral Tegmental Area / Q000737:chemistry / Q000166:cytology / Q000502:physiology
D001030:Apamin; D001640:Bicuculline; D002118:Calcium; D004298:Dopamine; D018690:Excitatory Amino Acid Agonists; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D016202:N-Methylaspartate; D010852:Picrotoxin; D011188:Potassium; D015221:Potassium Channels; D013779:Tetrodotoxin; C017069:bicuculline methiodide