17{beta}-Estradiol restores excitability of a sexually dimorphic subset of myelinated vagal afferents in ovariectomized rats

doi:10.1152/ajpcell.00059.2009

17β-Estradiol restores excitability of a sexually dimorphic subset of myelinated vagal afferents in ovariectomized rats

Guo-Fen Qiao,¹^,2^,* Bai-Yan Li,²^,3^,* Yan-Jie Lu,² Yi-Li Fu,¹ and John H. Schild³

¹Department of Biomedical Devices and Engineering, School of Life Science, Harbin Technological University, Harbin, China; ²Department of Pharmacology, Harbin Medical University, Harbin, China; and ³Department of Biomedical Engineering, School of Engineering and Technology, Indiana University-Purdue University, Indianapolis, Indiana

Submitted 2 February 2009 ; accepted in final form 22 June 2009

We recently identified a myelinated vagal afferent subpopulation(Ah type) far more prevalent in female than male rats and showedthat this difference extends to functionally specific visceralsensory afferents, baroreceptors of the aortic arch. Excitabilityof myelinated Ah-type afferents is markedly reduced after ovariectomy(OVX). Here we tested the hypothesis that 17β-estradiolcan selectively restore excitability of these sex-specific vagalafferents. Acutely isolated vagal afferent neurons (VGN) fromintact and OVX adult female rats were used with patch-clamptechnique and current-clamp protocols to assess the effect ofacute application of 17β-estradiol on neuronal excitability.At over physiologically relevant 17β-estradiol concentrationsfor rat (1–10 nM) excitability of myelinated Ah-type vagalafferents is restored to discharge frequencies comparable tothose in intact females, albeit with some interesting differencesrelated to burst and sustained patterns of neuronal discharge.Restoration of excitability occurs within 3 min of hormone applicationand is stereo specific, because 1,000 nM 17 ${alpha}$ -estradiol failsto alter excitability. Furthermore, activation of G protein-coupledestrogen receptor GPR30 with highly selective agonist G-1 similarlyrestores excitability of Ah-type afferents. The effectivenessof 17β-estradiol and G-1 is completely eliminated by applicationof high-affinity estrogen receptor ligand ICI-182,780. 17β-Estradiolconjugated with BSA is $~$ 70% as effective as 17β-estradiolalone in restoring Ah-type VGN excitability. These data supportour conclusions that the cellular mechanisms leading to rapidrestoration of neuronal excitability of myelinated Ah-type VGNafter OVX occur, at least in part, via membrane-bound estrogenreceptors. We contend that recovery of high-frequency dischargeat physiologically relevant 17β-estradiol concentrationsimplies that this unique subtype of low-threshold myelinatedvagal afferent may account for some of the sex-related differencesin visceral organ system function. Sex differences in cardiovascularand gastrointestinal function and the potential role of GPR30in modulation of sex-specific myelinated Ah-type vagal afferentsare discussed.

sensory afferent; visceral afferent; estrogen receptor; GPR30; ovariectomy

Addresses for reprint requests and other correspondence: J. H. Schild, Dept. of Biomedical Engineering, School of Engineering and Technology, Indiana Univ.-Purdue Univ., Indianapolis, IN 46202 (e-mail: jschild{at}iupui.edu); Y.-L. Fu, Dept. of Biomedical Devices and Engineering, School of Life Science, Harbin Technological Univ., Harbin, China (e-mail: liyu{at}hrtu.edu.cn).