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 3mM kynurenic acid and 10μM SR95531. In these conditions, baclofen (30μM), 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 3μM 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 Ca²⁺ influxes passing through presynaptic N- and P/Q-type Ca²⁺ 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 100μM SQ22536, an adenylyl cyclase inhibitor, or 1mM Ba²⁺, a G-protein coupled inwardly rectifying K⁺ channel blocker. During the train stimulation (10 pulses at 20Hz), which caused a marked synaptic depression of glycinergic IPSCs, baclofen at a 30μM concentration completely blocked glycinergic synaptic depression, but at a 3μM 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.

Keywords: GABA_B receptor, Substantia gelatinosa, Glycinergic IPSCs, Presynaptic inhibition, Pain