SKF97541 inhibits spinal sacral dorsal commissural nucleus neurons of the rat

Aim: To investigate the possible actions of SKF97541, a selective GABA _B receptor agonist, on sacral dorsal commissural nucleus (SDCN) neurons of spinal cord. Methods: Conventional whole-cell recordings were conducted on SDCN neurons of acute spinal cord slice. Actions of SKF97541 on membrane potentials and action potential firing were investigated under current-clamp mode, glutamatergic synaptic transmission was checked under voltage-clamp mode. Results: SDCN neurons membrane potentials were hyperpolarized and action potential firings were decreased by SKF97541 (0.5 μmol·L^-1) treatment. SKF97541 reduced frequency but not amplitude of glutamate-mediated miniature excitatory postsynaptic currents (mEPSCs), indicating a presynaptic inhibition. Presynaptic stimulation induced evoked postsynaptic potential (ePSPs). The amplitude of ePSPs was reduced by SKF97541, with an increase of paired-pulse ratio (PPR). All the above SKF97541 actions were largely abolished by a selective GABA_B receptor antagonist, CGP52432, indicating SKF97541 action via GABA_B receptors. Conclusions: SKF97541 directly inhibits SDCN neurons by suppressing postsynaptic neuronal excitability and action potential firing. On the other hand, SKF97541 presynaptically inhibits glutamate release. Thus SKF97541 may modulate pain signal transmission and modulation at SDCN.