Submitted on February 2, 2009
Revised on June 1, 2009
Accepted on June 22, 2009
17
-estradiol restores the excitability of a sexually dimorphic subset of myelinated vagal afferents in ovariectomized rats
Guo-Fen Qiao1, Bai-Yan Li2, Yan-Jie Lu1, Yi-Li Fu3, and John H. Schild2*
1 Harbin Medical University, Harbin, China
2 Indiana University Purdue University Indianapolis
3 School of Life Science, Harbin Technological University, Harbin, China
* To whom correspondence should be addressed. E-mail: jschild{at}iupui.edu.
We have recently identified a subpopulation of myelinated vagal afferents (Ah-type) that are far more prevalent in female than male rats. The excitability of myelinated Ah-type afferents is markedly reduced following ovariectomy (OVX). Here, we test the hypothesis that 17
-estradiol can selectively restore the excitability of these sex specific vagal afferents. Acutely isolated vagal afferent neurons (VGN) from intact and OVX adult female rats are used in conjunction with the patch clamp technique and current clamp protocols to assess the effect of acute application of 17-estradiol upon neuronal excitability. We show that at over physiologically relevant 17-estradiol concentrations for rat (1 - 10 nM) the excitability of myelinated Ah-type vagal afferents is restored to discharge frequencies comparable to those observed in intact females, albeit with some interesting differences related to burst and sustained patterns of neuronal discharge. Furthermore, activation of the G protein-coupled estrogen receptor GPR30 using the highly selective agonist G-1 similarly restores the excitability of Ah-type afferents. The effectiveness of 17-estradiol and G-1 is eliminated by application of ICI 182,780. 17-estradiol conjugated with bovine serum albumin is 
70% as effective as 17-estradiol alone in restoring Ah-type VGN excitability. Collectively, these data support our conclusions that the cellular mechanisms leading to the rapid restoration of neuronal excitability of myelinated Ah-type VGN following OVX occurs, at least in part, by way of membrane bound estrogen receptors. We contend that recovery of high frequency discharge at physiologically relevant concentrations of 17-estradiol implies this unique subtype of low threshold myelinated vagal afferent may account for some of the noted sex related differences in visceral organ system function. The recognized sex differences in cardiovascular and gastrointestinal function and the potential role the G protein-coupled receptor GPR30 may have upon the modulation of sex specific myelinated Ah-type vagal afferents are discussed.
