Glycinergic and GABAergic inhibitory transmission are affected by phospholipase A₂ activation in a manner different from each other in adult rat substantia gelatinosa neurons

Abstract

We have previously reported that a phospholipase A₂ (PLA₂) activator melittin enhances excitatory and inhibitory synaptic transmission in substantia gelatinosa (SG) neurons of adult rat spinal cord slices. The present study examined a detail of a difference in pharmacology between the melittin-induced enhancements of glycinergic and GABAergic spontaneous inhibitory postsynaptic currents (sIPSCs) recorded at 0 mV by using the whole-cell patch-clamp technique. The enhancements of the frequency and the amplitude of GABAergic but not glycinergic sIPSC produced by melittin (1 μM) superfused for 3 min were largely reduced in extent in the presence of a Na⁺-channel blocker tetrodotoxin (0.5 μM). The effects of melittin on glycinergic sIPSCs were also resistant to a non-NMDA receptor antagonist CNQX (10 μM) while being depressed to a great extent by a PLA₂ inhibitor 4-bromophenacyl bromide (10-50 μM). These effects of melittin on glycinergic sIPSC amplitude and frequency were dose-dependent with EC₅₀ values of about 0.7 μM. These results indicate that PLA₂ activation results in enhancing GABAergic and glycinergic transmission in a different manner in such that the former but not latter effect is possibly mediated by the enhancement of excitatory transmission by PLA₂ activation which is followed by the release of neuromodulators such as acetylcholine and norepinephrine involved in enhancing GABAergic transmission. [J Physiol Sci. 2007;57 Suppl:S148]