Melittin-induced enhancement of GABAergic but not glycinergic inhibitory transmission in rat spinal dorsal horn neurons is mediated by acetylcholine and norepinephrine

Abstract

We have reported that melittin enhances excitatory and inhibitory transmission in substantia gelatinosa (SG) neurons of the spinal cord by activating phospholipase A₂ (PLA₂). Melittin-induced enhancement of GABAergic but not glycinergic inhibitory transmission was sensitive to a Na⁺-channel blocker tetrodotoxin, and glutamate receptor antagonists. In order to know more the difference in melittin action between GABAergic and glycinergic transmission, we examined the effect of melittin (1 μM) on GABAergic and glycinergic spontaneous IPSCs (sIPSCs) recorded under various conditions by applying the whole-cell patch-clamp technique to SG neurons of an adult rat spinal cord slice. Melittin superfused for 3 min increased the amplitude and frequency of glycinergic but not GABAergic sIPSC in a nominally Ca²⁺-free solution. The enhancement of GABAergic but not glycinergic transmission was reduced in extent by nicotinic (mecamylamine, 20 μM), muscarinic ACh-receptor antagonist (atropine, 1 μM) or α₁-adrenoceptor antagonist (WB-4101, 0.5 μM). These results indicate that glycinergic transmission is enhanced by a direct action of melittin at glycinergic synapses while GABAergic transmission enhancement produced by melittin is mediated by nicotinic and muscarinic ACh receptors, and α₁-adrenoceptors. It is suggested that PLA₂ activation modulates nociceptive transmission by enhancing each of GABAergic and glycinergic transmission in a different manner. [J Physiol Sci. 2008;58 Suppl:S134]