Bicuculline methiodide potentiates NMDA-dependent burst firing in rat dopamine neurons by blocking apamin-sensitive Ca2+-activated K+ currents

Steven Johnson, Vincent Seutin

Research output: Contribution to journalArticle

140 Citations (Scopus)

Abstract

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 μM) 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 (10μM) 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 (100μM) and bicuculline free base (30 μM) blocked the inhibition of firing produced by the GABA(A) agonist isoguvacine (100μM), neither had apamin-like effects. We conclude that BMI potentiates burst firing by blocking an apamin-sensitive Ca2+-activated K+ current.

Original languageEnglish (US)
Pages (from-to)13-16
Number of pages4
JournalNeuroscience Letters
Volume231
Issue number1
DOIs
StatePublished - Aug 1 1997

Fingerprint

Apamin
Dopaminergic Neurons
N-Methylaspartate
GABA-A Receptor Agonists
Bee Venoms
Picrotoxin
Bicuculline
Microelectrodes
GABA-A Receptors
Mesencephalon
bicuculline methiodide

Keywords

  • Apamin
  • Brain slice
  • Burst firing
  • Dopamine neuron
  • N-methyl-D- aspartate
  • Picrotoxin
  • Substantia nigra
  • Ventral tegmental area

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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title = "Bicuculline methiodide potentiates NMDA-dependent burst firing in rat dopamine neurons by blocking apamin-sensitive Ca2+-activated K+ currents",
abstract = "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 μM) 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 (10μM) 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 (100μM) and bicuculline free base (30 μM) blocked the inhibition of firing produced by the GABA(A) agonist isoguvacine (100μM), neither had apamin-like effects. We conclude that BMI potentiates burst firing by blocking an apamin-sensitive Ca2+-activated K+ current.",
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AU - Seutin, Vincent

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N2 - 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 μM) 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 (10μM) 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 (100μM) and bicuculline free base (30 μM) blocked the inhibition of firing produced by the GABA(A) agonist isoguvacine (100μM), neither had apamin-like effects. We conclude that BMI potentiates burst firing by blocking an apamin-sensitive Ca2+-activated K+ current.

AB - 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 μM) 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 (10μM) 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 (100μM) and bicuculline free base (30 μM) blocked the inhibition of firing produced by the GABA(A) agonist isoguvacine (100μM), neither had apamin-like effects. We conclude that BMI potentiates burst firing by blocking an apamin-sensitive Ca2+-activated K+ current.

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