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Browsing by Author "Yan, Zhen-Yu"
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Item Gender Differences in Histamine-Induced Depolarization and Inward Currents in Vagal Ganglion Neurons in Rats(Ivyspring, 2013-11-20) Li, Jun-Nan; Qian, Zhao; Xu, Wen-Xiao; Xu, Bing; Lu, Xiao-Long; Yan, Zhen-Yu; Han, Li-Min; Liu, Yang; Yuan, Mei; Schild, John; Qiao, Guo-Fen; Li, Bai-Yan; Biomedical Engineering, Purdue School of Engineering and TechnologyEvidence 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.Item Na+-induced Ca2+ influx through reverse mode of Na+-Ca2+ exchanger in mouse ventricular cardiomyocyte(Oncotarget, 2015-09-15) Yan, Zhen-Yu; Ban, Tao; Fan, Tao; Chen, Wei-Ran; Sun, Hong-Li; Chen, Hanying; Qiao, Quo-Fen; Li, Bai-Yan; Department of Pediatrics, IU School of MedicineBACKGROUND: Dobutamine is commonly used for clinical management of heart failure and its pharmacological effects have long been investigated as inotropics via β-receptor activation. However, there is no electrophysiological evidence if dobutamine contributes inotropic action due at least partially to the reverse mode of Na+-Ca2+ exchanger (NCX) activation. METHODS: Action potential (AP), voltage-gated Na+ (INa), Ca2+ (ICa), and K+ (Ito and IK1) currents were observed using whole-cell patch technique before and after dobutamine in ventricular cardiomyocytes isolated from adult mouse hearts. Another sets of observation were also performed with Kb-r7943 or in the solution without [Ca2+]o. RESULTS: Dobutamine (0.1-1.0 μM) significantly enhanced the AP depolarization with prolongation of AP duration (APD) in a concentration-dependent fashion. The density of INa was also increased concentration-dependently without alternation of voltage-dependent steady-status of activation and inactivation, reactivation as well. Whereas, the activities for ICa, Ito, and IK1 were not changed by dobutamine. Intriguingly, the dobutamine-mediated changes in AP repolarization were abolished by 3 μM Kb-r7943 pretreatment or by simply removing [Ca2+]o without affecting accelerated depolarization. Additionally, the ratio of APD50/APD90 was not significantly altered in the presence of dobutamine, implying that effective refractory period was remain unchanged. CONCLUSIONS: This novel finding provides evidence that dobutamine upregulates of voltage-gated Na+ channel function and Na+ influx-induced activation of the reverse mode of NCX, suggesting that dobutamine may not only accelerate ventricular contraction via fast depolarization but also cause Ca2+ influx, which contributes its positive inotropic effect synergistically with β-receptor activation without increasing the arrhythmogenetic risk.Item Subtype Identification in Acutely Dissociated Rat Nodose Ganglion Neurons Based on Morphologic Parameters(Ivyspring, 2013-07-27) Lu, Xiao-Long; Xu, Wen-Xiao; Yan, Zhen-Yu; Qian, Zhao; Xu, Bing; Liu, Yang; Han, Li-Min; Gao, Rui-Chen; Li, Jun-Nan; Yuan, Mei; Zhao, Chong-Bao; Qiao, Guo-fen; Li, Bai-Yan; Pediatrics, School of MedicineNodose ganglia are composed of A-, Ah- and C-type neurons. Despite their important roles in regulating visceral afferent function, including cardiovascular, pulmonary, and gastrointestinal homeostasis, information about subtype-specific expression, molecular identity, and function of individual ion transporting proteins is scarce. Although experiments utilizing the sliced ganglion preparation have provided valuable insights into the electrophysiological properties of nodose ganglion neuron subtypes, detailed characterization of their electrical phenotypes will require measurements in isolated cells. One major unresolved problem, however, is the difficulty to unambiguously identify the subtype of isolated nodose ganglion neurons without current-clamp recording, because the magnitude of conduction velocity in the corresponding afferent fiber, a reliable marker to discriminate subtypes in situ, can no longer be determined. Here, we present data supporting the notion that application of an algorithm regarding to microscopic structural characteristics, such as neuron shape evaluated by the ratio between shortest and longest axis, neuron surface characteristics, like membrane roughness, and axon attachment, enables specific and sensitive subtype identification of acutely dissociated rat nodose ganglion neurons, by which the accuracy of identification is further validated by electrophysiological markers and overall positive predictive rates is 89.26% (90.04%, 76.47%, and 98.21% for A-, Ah, and C-type, respectively). This approach should aid in gaining insight into the molecular correlates underlying phenotypic heterogeneity of nodose ganglia. Additionally, several critical points that help for neuron identification and afferent conduction calibration are also discussed.