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Int J Biol Sci 2013; 9(10):1079-1088. doi:10.7150/ijbs.7595

Research Paper

Gender Differences in Histamine-Induced Depolarization and Inward Currents in Vagal Ganglion Neurons in Rats

Jun-Nan Li1, Zhao Qian1, Wen-Xiao Xu2, Bing Xu1, Xiao-Long Lu1, Zhen-Yu Yan1, Li-Min Han1, Yang Liu1, 3, Mei Yuan3, John Schild4, Guo-Fen Qiao1, 3✉, Bai-Yan Li1, 4✉

1. Department of Pharmacology, Harbin Medical University, Harbin, China,
2. Dept. of Orthopedics, the First Affiliated Hospital, Harbin Medical University, Harbin, China,
3. Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, Harbin Medical University, Harbin, China
4. Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, USA

Abstract

Evidence has shown gender differences regarding the critical roles of histamine in the prevalence of asthma, anaphylaxis, and angina pectoris. Histamine depolarizes unmyelinated C-type neurons without any effects on myelinated A-type vagal ganglion neurons (VGNs) in male rats. However, little is known if VGNs from females react to histamine in a similar manner. Membrane depolarization and inward currents were tested in VGNs isolated from adult rats using a whole-cell patch technique. Results from males were consistent with the literature. Surprisingly, histamine-induced depolarization and inward currents were observed in both unmyelinated C-type and myelinated A- and Ah-type VGNs from female rats. In Ah-type neurons, responses to 1.0 μM histamine were stronger in intact females than in males and significantly reduced in ovariectomized (OVX) females. In C-type neurons, histamine-induced events were significantly smaller (pA/pF) in intact females compared with males and this histamine-induced activity was dramatically increased by OVX. Female A-types responded to histamine, which was further increased following ovariectomy. Histamine at 300 nM depolarized Ah-types in females, but not Ah-types in OVX females. In contrast, the sensitivity of A- and C-types to histamine was upregulated by OVX. These data demonstrate gender differences in VGN chemosensitivity to histamine for the first time. Myelinated Ah-types showed the highest sensitivity to histamine across female populations, which was changed by OVX. These novel findings improve the understanding of gender differences in the prevalence of asthma, anaphylaxis, and pain. Changes in sensitivity to histamine by OVX may explain alterations in the prevalence of certain pathophysiological conditions when women reach a postmenopausal age.

Keywords: chemosensitivity, histamine, vagal afferent neuron, membrane depolarization, inward current, whole-cell patch.

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How to cite this article:
Li JN, Qian Z, Xu WX, Xu B, Lu XL, Yan ZY, Han LM, Liu Y, Yuan M, Schild J, Qiao GF, Li BY. Gender Differences in Histamine-Induced Depolarization and Inward Currents in Vagal Ganglion Neurons in Rats. Int J Biol Sci 2013; 9(10):1079-1088. doi:10.7150/ijbs.7595. Available from http://www.ijbs.com/v09p1079.htm