SKF97541抑制大鼠骶髓后联合核神经元

目的研究GABAB受体特异性激动剂SKF97541对骶髓后联合核(SDCN)神经元的作用。方法在大鼠骶段脊髓横切薄片上,利用全细胞膜片钳法记录骶髓后联合核神经元。电流钳记录模式下,观察SKF97541对神经元膜电位和动作电位发放的影响。电压钳模式下,观察谷氨酸能兴奋性突触后电流(EPSCs)对SKF97541处理的变化。结果SKF97541(0.5μmol.L-1)通过作用于GABAB受体,减少SDCN神经元动作电位发放,同时促进细胞膜超极化。SKF97541在电压钳模式下,减少谷氨酸介导的微小EPSCs的频率,但对振幅无影响,提示SKF97541通过作用于突触前GABAB受体抑制谷氨酸释放。突触前刺激引起的突触后电位,也被SKF97541抑制。结论在骶髓后联合核,SKF97541通过作用于突触后GABAB受体,直接抑制神经元的兴奋性和动作电位发放;并通过突触前GABAB受体,抑制谷氨酸的释放。以上结果提示SKF97541的抑制作用可能抑制骶髓后联合核神经元对伤害性信息的传递。

SKF97541 inhibits spinal sacral dorsal commissural nucleus neurons of the rat

Aim To investigate the possible actions of SKF97541,a selective GABAB 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 GABAB receptor antagonist,CGP52432,indicating SKF97541 action via GABAB 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.