Blockade of GABA(B) receptors facilitates evoked neurotransmitter release at spinal dorsal horn synapse.

K Yang, H Ma

Index: Neuroscience 193 , 411-20, (2011)

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Abstract

Metabotropic GABA type B (GABA(B)) receptors are abundantly expressed in the rat spinal dorsal horn. Activation of GABA(B) receptors by exogenous agonists inhibits synaptic transmission, which is believed to underlie the GABA(B) receptor-mediated analgesia. However, little effort has been made to test whether endogenous GABA might also mediate inhibition by acting on GABA(B) receptors. In this study, whole-cell recording techniques were employed to study the effect of endogenous GABA on GABA(B) receptors in substantia gelatinosa (SG) neurons in adult rat spinal cord slices. In current-clamp mode, blockade of GABA(B) receptors by their selective antagonist 3-[[[(3,4-dichlorophenyl)methyl]amino]propyl] (diethoxy-methyl) phosphinic acid (CGP 52432) facilitated presynaptic stimulation-induced action potential discharge and increased amplitude of postsynaptic potentials (PSPs), meaning a GABA(B) receptor-mediated inhibition of SG neuron excitability. In voltage-clamp mode, blockade of GABA(B) receptors increased the amplitude of evoked excitatory postsynaptic currents (eEPSCs) and decreased paired-pulse ratio, indicating a presynaptic CGP 52432 action. Primary afferent Aδ or C fiber-evoked EPSCs were also facilitated by CGP 52432 application. Amplitudes of evoked GABAergic and glycinergic inhibitory postsynaptic currents (eIPSCs) were enhanced by GABA(B) receptor blockade. The facilitation of amplitude persisted in the presence of a specific GABA transporter 1 (GAT-1) blocker, tiagabine, or GAT-2/3 blocker SNAP5114. However, blockade of GABA(B) receptors had no effect on action potential-independent miniature EPSCs (mEPSCs), miniature IPSCs (mIPSCs), or membrane conductance. Taken together, these results suggest that endogenous GABA modulates evoked synaptic transmission in SG neurons by acting on GABA(B) receptors. This GABA(B) receptor-mediated homeostatic regulation of neuronal excitability and neurotransmitter release might contribute to modulation of nociception in spinal dorsal horn.Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.