GABA B receptor-mediated presynaptic inhibition of glycinergic transmission onto substantia gelatinosa neurons in the rat spinal cord

Abstract

The GABA B receptor-mediated presynaptic inhibition of glycinergic transmission was studied from young rat substantia gelatinosa (SG) neurons using a conventional whole-cell patch clamp technique. Action potential-dependent glycinergic inhibitory postsynaptic currents (IPSCs) were recorded from SG neurons in the presence of 3 mM kynurenic acid and 10 μM SR95531. In these conditions, baclofen (30 μM), a selective GABA B receptor agonist, greatly reduced the amplitude of glycinergic IPSCs and increased the paired-pulse ratio. Such effects were completely blocked by 3 μM CGP55845, a selective GABA B receptor antagonist, indicating that the activation of presynaptic GABA B receptors decreases glycinergic synaptic transmission. Glycinergic IPSCs were largely dependent on Ca 2+ influxes passing through presynaptic N- and P/Q-type Ca 2+ channels, and these channels contributed equally to the baclofen-induced inhibition of glycinergic IPSCs. However, the baclofen-induced inhibition of glycinergic IPSCs was not affected by either 100 μM SQ22536, an adenylyl cyclase inhibitor, or 1 mM Ba 2+, a G-protein coupled inwardly rectifying K + channel blocker. During the train stimulation (10 pulses at 20 Hz), which caused a marked synaptic depression of glycinergic IPSCs, baclofen at a 30 μM concentration completely blocked glycinergic synaptic depression, but at a 3 μM concentration it largely preserved glycinergic synaptic depression. Such GABA B receptor-mediated dynamic changes in short-term synaptic plasticity of glycinergic transmission onto SG neurons might contribute to the central processing of sensory signals.