Involvement of the GABAergic system for Ptychodiscus brevis toxin-induced depression of synaptic transmission elicited in isolated spinal cord from neonatal rats

Abstract

The involvement of inhibitory transmitters for Ptychodiscus brevis toxin (PbTx)-induced depression of spinal synaptic transmission in neonatal rats was investigated. Stimulation of a dorsal root evoked monosynaptic reflex (MSR) and polysynaptic reflex (PSR) potentials in the segmental ventral root. The PbTx depressed the reflexes in a concentration-dependent manner and the depression was blocked by GABA A antagonist, bicuculline (1 μM). GABA also produced depression of the reflexes in a concentration-dependent manner. Simultaneous application of submaximal concentrations of PbTx (28 μM) and GABA (30 μM) enhanced the depression (>75%). In contrast, PbTx alone (28 μM) depressed the MSR and the PSR by 33 and 47%, respectively, and GABA (30 μM) alone depressed the reflexes by 30%. The N-methyl- d-aspartate receptor antagonist, dl-2-amino-5-phosphono-pentanoic acid (10 μM), blocked the PbTx-induced depression of MSR and also the enhancement of GABA response by PbTx. A glycine receptor antagonist, strychnine (1 μM), failed to block the depression by the toxin up to 28 μM; however, the depression was attenuated significantly at 84 μM of the toxin. The results indicate that PbTx depressed the spinal reflexes via GABA A receptors. Furthermore, the potentiation of GABAergic action by PbTx requires the N-methyl- d-aspartate dependent mechanism.