Glycine receptor in rat hippocampal and spinal cord neurons as a molecular target for rapid actions of 17-β-estradiol

摘要: Glycine receptors (GlyRs) play important roles in regulating hippocampal neural network activity and spinal nociception. Here we show that, cultured rat (HIP) dorsal horn (SDH) neurons, 17-β-estradiol (E2) rapidly reversibly reduced the peak amplitude of whole-cell glycine-activated currents (IGly). In outside-out membrane patches from HIP neurons devoid nuclei, E2 similarly inhibited IGly, suggesting a non-genomic characteristic. Moreover, effect on IGly persisted presence calcium chelator BAPTA, protein kinase inhibitor staurosporine, classical ER (i.e. ERα ERβ) antagonist tamoxifen, or G-protein modulators, favoring direct action GlyRs. HEK293 cells expressing various combinations GlyR subunits, only affected α2, α2β α3β that either α2-containing α3β-GlyRs mediate observed neurons. Furthermore, GlyR-mediated tonic current pyramidal CA1 region, where abundant α2 subunit is expressed. We suggest neuronal novel molecular target which directly inhibits function GlyRs SDH regions. This finding may shed new light premenstrual dysphoric disorder gender differences pain sensation at CNS level.