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

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 microM). GABA also produced depression of the reflexes in a concentration-dependent manner. Simultaneous application of submaximal concentrations of PbTx (28 microM) and GABA (30 microM) enhanced the depression (>75%). In contrast, PbTx alone (28 microM) depressed the MSR and the PSR by 33 and 47%, respectively, and GABA (30 microM) alone depressed the reflexes by 30%. The N-methyl-D-aspartate receptor antagonist, DL-2-amino-5-phosphono-pentanoic acid (10 microM), blocked the PbTx-induced depression of MSR and also the enhancement of GABA response by PbTx. A glycine receptor antagonist, strychnine (1 microM), failed to block the depression by the toxin up to 28 microM; however, the depression was attenuated significantly at 84 microM 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.