The GABAB antagonist phaclofen inhibits the late K+-dependent IPSP in cat and rat thalamic and hippocampal neurones

doi:10.1016/0006-8993(88)91275-9

Brain Research

Volume 448, Issue 2, 17 May 1988, Pages 351-354

https://doi.org/10.1016/0006-8993(88)91275-9 Get rights and content

Abstract

Phaclofen (0.5–1 mM) reversibly inhibited the late, bicuculline resistant, K⁺ dependent IPSP recorded in projection cells of the cat and rat dorsal lateral geniculate nucleus and in rat hippocampal CA1 pyramidal neurones. At the same concentrations, phaclofen reversibly blocked the K⁺ dependent, bicuculline insensitive hyperpolarization evoked by GABA and baclofen but had no effect on the GABA_A IPSP. These results represent conclusive evidence that GABA_B receptors mediate the late K⁺ dependent IPSP in cortical and subcortical neurones.

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γ-Aminobutyric acid B (GABA_B) receptors are G-protein-coupled receptors that have an inhibitory effect at both pre- and postsynaptic sites. They exist as heterodimers, with the GABA_B(1) subunit responsible for ligand binding and G-protein activation mediated by the GABA_B(2) subunit. GABA_B receptors couple to G_i/o G-proteins, resulting in activation of K⁺ channels, inhibition of Ca²⁺ channels, and inhibition of adenylyl cyclase, reducing cyclic adenosine monophosphate levels. GABA_B receptor effects include postsynaptic membrane hyperpolarization and reduction in neurotransmitter release. These receptors are important for normal brain function, regulating the induction of synaptic plasticity and suppression of overexcitation of neuronal circuits.
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^∗: Present address: MRC Anatomical Neuropharmacology Unit, Department of Pharmacology, Oxford University, South Parks Road, Oxford OX1 3QT, U.K.

^∗∗: Present address: Department des Neurosciences de la Vision, Institut des Neurosciences, Université Pierre et Marie Curie, 4 Place Jussieu, Paris Cedex 05, France.

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Short communicationThe GABAB antagonist phaclofen inhibits the late K+-dependent IPSP in cat and rat thalamic and hippocampal neurones

Abstract

Neuroscience

J. Neurosci. Methods

Brain Research

Neuroscience

Neurosci. Lett.

Characteristics of a slow hyperpolarizing synaptic potential in rat hippocampal pyramidal cells

J. Neurophysiol.

A G protein couples serotonin and GABAB receptors to the same channels in hippocampus

Science

Neocortex: cellular properties and intrinsic circuitry

Intracellular recorded synaptic antagonism in the rat dentate gyrus

Nature (Lond.)

Two types of ipsps recorded in projection cells of the rat lateral geniculate nucleus in vitro

J. Physiol. (Lond.)

Short communication
The GABA_B antagonist phaclofen inhibits the late K⁺-dependent IPSP in cat and rat thalamic and hippocampal neurones

A G protein couples serotonin and GABA_B receptors to the same channels in hippocampus