Mechanisms of modulation of pregnanolone on glycinergic response in cultured spinal dorsal horn neurons of rat

P. Jiang, C. X. Yang, Y. T. Wang, T. L. Xu

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

The glycine receptors and neurosteroids in spinal cord are both implicated in nociceptive signal processing. However, the modulatory effects of neurosteroid pregnanolone (5β-pregnan-3α-ol-20-one) on native glycine receptors remain unclear. In the present study, we examined the effects of pregnanolone and its three isomers on glycine receptors by using whole-cell patch-clamp technique. Our results showed that pregnanolone reversibly inhibited the amplitude of glycine-induced current mediated by native glycine receptors and recombinant α1-, α2-, α3- and α1β-glycine receptors. In cultured spinal dorsal horn neurons of rats, pregnanolone inhibited the glycine-induced current in dose-dependent manner, with an antagonist concentration inducing half-maximal response of 1.0±0.3 μM. The inhibitory effect of pregnanolone on glycine-induced current was voltage-independent and pregnanolone shifted the concentration-response curve for glycine-induced current rightward in a parallel manner without altering the maximal value and Hill coefficient. The isomer of pregnanolone, allopregnanolone (5α-pregnan-3α-ol-20-one) slightly enhanced glycine-induced current, whereas iso-pregnanolone (5β-pregnan-3β-ol-20-one) and iso-allopregnanolone (5α-pregnan-3β-ol-20-one) did not affect the glycine-induced current significantly in cultured spinal dorsal horn neurons. Thus, our results suggest that the inhibitory effect of pregnanolone on glycine-induced current is of a competitive type and depends on the stereo structure of pregnanolone. Furthermore, pregnanolone decreased the amplitude and frequency of the glycinergic miniature inhibitory postsynaptic currents. Through modulating the glycinergic inhibitory neurotransmission, pregnanolone may affect the nociceptive sensory processing under physiological and pathological conditions.

Original languageEnglish (US)
Pages (from-to)2041-2050
Number of pages10
JournalNeuroscience
Volume141
Issue number4
DOIs
StatePublished - Aug 21 2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Keywords

  • cultured spinal dorsal horn neurons of rat
  • glycinergic mIPSCs
  • native and recombinant glycine receptor
  • nociception
  • pregnanolone
  • whole-cell patch-clamp recording

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