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

doi:10.1016/S0304-3940(97)00508-9

Neuroscience Letters

Volume 231, Issue 1, 1 August 1997, Pages 13-16

https://doi.org/10.1016/S0304-3940(97)00508-9 Get rights and content

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

Section snippets

Acknowledgements

This study was funded by PHS grant MH40416. We wish to thank B. Anna McCoy for her helpful comments.

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Local application of bicuculline methiodide produced a modest but statistically significant 25% increase in firing rate (Paladini and Tepper, 1999; Tepper et al., 1995). Two other GABAA antagonists that do not block the SK channel (as does bicuculline methiodide, Johnson and Seutin, 1997), PTX and gabazine, exerted smaller, less consistent excitatory effects on firing rate (Paladini and Tepper, 1999). Local application of the selective GABAB receptor antagonists, 2-OH-saclofen or CGP55845A, exerted even more modest, but opposite effects on firing rate, producing small decreases in spontaneous activity (Paladini and Tepper, 1999; Tepper et al., 1995).
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Bicuculline methiodide potentiates NMDA-dependent burst firing in rat dopamine neurons by blocking apamin-sensitive Ca2+-activated K+ currents

Abstract

Section snippets

Acknowledgements

Neuroscience

Brain Res.

Methods Enzymol.

Brain Res.

Brain Res.

Brain Res.

Single apamin-blocked Ca-activated K+ channels of small conductance in cultured rat skeletal muscle

Nature

Inhibition of acetylcholinesterase by bicuculline and related alkaloids

J. Neurochem.

Electrophysiological analysis of the actions of strychnine, bicuculline and picrotoxin on the axonal membrane

J. Neurobiol.

Morphology and electrophysiological properties of immunocytochemically identified rat dopamine neurons recorded in vitro

J. Neurosci.

Bicuculline: a convulsant with synaptic and nonsynaptic actions

Neurology

Apamin as a selective blocker of the calcium-dependent potassium channel in neuroblastoma cells: voltage-clamp and biochemical characterization of the toxin receptor

Proc. Natl. Acad. Sci. USA

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

Single apamin-blocked Ca-activated K⁺ channels of small conductance in cultured rat skeletal muscle