Jiang, P (reprint author), Chinese Acad Sci, Inst Neurosci, Shanghai 200031, Peoples R China,email@example.com
Glycine receptors (GlyRs) play important roles in regulating hippocampal neural network activity and spinal nociception. Here we show that, in cultured rat hippocampal (HIP) and spinal dorsal horn (SDH) neurons, 17-beta-estradiol (E-2) rapidly and reversibly reduced the peak amplitude of whole-cell glycine-activated currents (I-Gly). In outside-out membrane patches from HIP neurons devoid of nuclei, E-2 similarly inhibited I-Gly, suggesting a non-genomic characteristic. Moreover, the E-2 effect on IGly persisted in the presence of the calcium chelator BAPTA, the protein kinase inhibitor staurosporine, the classical ER (i. e. ER alpha and ER beta) antagonist tamoxifen, or the G-protein modulators, favoring a direct action of E-2 on GlyRs. In HEK293 cells expressing various combinations of GlyR subunits, E-2 only affected the I-Gly in cells expressing alpha 2, alpha 2 beta or alpha 3 beta subunits, suggesting that either alpha 2- containing or alpha 3 beta-GlyRs mediate the E-2 effect observed in neurons. Furthermore, E-2 inhibited the GlyR-mediated tonic current in pyramidal neurons of HIP CAI region, where abundant GlyR alpha 2 subunit is expressed. We suggest that the neuronal GlyR is a novel molecular target of E-2 which directly inhibits the function of GlyRs in the HIP and SDH regions. This finding may shed new light on premenstrual dysphoric disorder and the gender differences in pain sensation at the CNS level.
Jiang, Peng; Kong, Yan; Zhang, Xiao-Bing; Wang, Wei; Liu, Chun-Feng; Xu, Tian-Le.Glycine receptor in rat hippocampal and spinal cord neurons as a molecular target for rapid actions of 17-beta-estradiol,MOLECULAR PAIN,2009,5():40941