AIM:To assess the role of hyperpolarization-activated cyclic nucleotide-gated cation(HCN) channels in regulating the excitability of vagal and spinal gut afferents.METHODS:The mechanosensory response of mesenteric aff...AIM:To assess the role of hyperpolarization-activated cyclic nucleotide-gated cation(HCN) channels in regulating the excitability of vagal and spinal gut afferents.METHODS:The mechanosensory response of mesenteric afferent activity was measured in an ex vivo murine jejunum preparation.HCN channel activity was recorded through voltage and current clamp in acutely dissociated dorsal root ganglia(DRG) and nodose ganglia(NG) neurons retrogradely labeled from the small intestine through injection of a fluorescent marker(DiI).The isoforms of HCN channels expressed in DRG and NG neurons were examined by immunohistochemistry.RESULTS:Ramp distension of the small intestine evoked biphasic increases in the afferent nerve activity,reflecting the activation of low-and high-threshold fibers.HCN blocker CsCl(5 mmol/L) preferentially inhibited the responses of low-threshold fibers to distension and showed no significant effects on the high-threshold responses.The effect of CsCl was mimicked by the more selective HCN blocker ZD7288(10 μmol/L).In 71.4% of DiI labeled DRG neurons(n = 20) and 90.9% of DiI labeled NG neurons(n = 10),an inward current(I h current) was evoked by hyperpolarization pulses which was fully eliminated by extracellular CsCl.In neurons expressing I h current,a typical "sag" was observed upon injection of hyperpolarizing current pulses in current-clamp recordings.CsCl abolished the sag entirely.In some DiI labeled DRG neurons,the I h current was potentiated by 8-Br-cAMP,which had no effect on the I h current of DiI labeled NG neurons.Immunohistochemistry revealed differential expression of HCN isoforms in vagal and spinal afferents,and HCN 2 and HCN 3 seemed to be the dominant isoform in DRG and NG,respectively.CONCLUSION:HCNs differentially regulate the excitability of vagal and spinal afferent of murine small intestine.展开更多
By taking the Yong River for example in this paper, based on the multiple measured data during 1957 to 2009, the change process of runoff, tide feature, tidal wave, tidal influx and sediment transport are analyzed. Th...By taking the Yong River for example in this paper, based on the multiple measured data during 1957 to 2009, the change process of runoff, tide feature, tidal wave, tidal influx and sediment transport are analyzed. Then a mathematical model is used to reveal the influence mechanism on hydrodynamic characteristics and sediment transport of the wading engineering groups such as a tide gate, a breakwater, reservoirs, bridges and wharves, which were built in different periods. The results showed the hydrodynamic characteristics and sediment transport of the Yong River changed obviously due to the wading engineering groups. The tide gate induced deformation of the tidal wave, obvious reduction of the tidal influx and weakness of the tidal dynamic, decrease of the sediment yield of flood and ebb tide and channel deposition. The breakwater blocked estuarine entrances, resulting in the change of the tidal current and the reduction of the tidal influx in the estuarine area. The large-scale reservoirs gradually made the decrease of the Yong River runoff. The bridge and wharf groups took up cross-section areas, the cumulative affection of which caused the increase of tidal level in the tidal river.展开更多
基金Supported by Science and Technology Commission of Shanghai Municipality,No. 10ZR1417300Educational Commission of Shanghai Municipality,No. 10ZZ69
文摘AIM:To assess the role of hyperpolarization-activated cyclic nucleotide-gated cation(HCN) channels in regulating the excitability of vagal and spinal gut afferents.METHODS:The mechanosensory response of mesenteric afferent activity was measured in an ex vivo murine jejunum preparation.HCN channel activity was recorded through voltage and current clamp in acutely dissociated dorsal root ganglia(DRG) and nodose ganglia(NG) neurons retrogradely labeled from the small intestine through injection of a fluorescent marker(DiI).The isoforms of HCN channels expressed in DRG and NG neurons were examined by immunohistochemistry.RESULTS:Ramp distension of the small intestine evoked biphasic increases in the afferent nerve activity,reflecting the activation of low-and high-threshold fibers.HCN blocker CsCl(5 mmol/L) preferentially inhibited the responses of low-threshold fibers to distension and showed no significant effects on the high-threshold responses.The effect of CsCl was mimicked by the more selective HCN blocker ZD7288(10 μmol/L).In 71.4% of DiI labeled DRG neurons(n = 20) and 90.9% of DiI labeled NG neurons(n = 10),an inward current(I h current) was evoked by hyperpolarization pulses which was fully eliminated by extracellular CsCl.In neurons expressing I h current,a typical "sag" was observed upon injection of hyperpolarizing current pulses in current-clamp recordings.CsCl abolished the sag entirely.In some DiI labeled DRG neurons,the I h current was potentiated by 8-Br-cAMP,which had no effect on the I h current of DiI labeled NG neurons.Immunohistochemistry revealed differential expression of HCN isoforms in vagal and spinal afferents,and HCN 2 and HCN 3 seemed to be the dominant isoform in DRG and NG,respectively.CONCLUSION:HCNs differentially regulate the excitability of vagal and spinal afferent of murine small intestine.
基金financially supported by the National Science Foundation for Distinguished Young Scholars of China(Grant No.51125034)the National Natural Science Foundation of China(Grant Nos.51279046 and 50909037)the Fundamental Research Funds for the Central Universities(Grant No.2010B01114)
文摘By taking the Yong River for example in this paper, based on the multiple measured data during 1957 to 2009, the change process of runoff, tide feature, tidal wave, tidal influx and sediment transport are analyzed. Then a mathematical model is used to reveal the influence mechanism on hydrodynamic characteristics and sediment transport of the wading engineering groups such as a tide gate, a breakwater, reservoirs, bridges and wharves, which were built in different periods. The results showed the hydrodynamic characteristics and sediment transport of the Yong River changed obviously due to the wading engineering groups. The tide gate induced deformation of the tidal wave, obvious reduction of the tidal influx and weakness of the tidal dynamic, decrease of the sediment yield of flood and ebb tide and channel deposition. The breakwater blocked estuarine entrances, resulting in the change of the tidal current and the reduction of the tidal influx in the estuarine area. The large-scale reservoirs gradually made the decrease of the Yong River runoff. The bridge and wharf groups took up cross-section areas, the cumulative affection of which caused the increase of tidal level in the tidal river.
文摘目的探讨房性心动过速与窦房结功能障碍的关系,研究其可能的发病机制。方法 30只成年新西兰兔随机分成实验组和对照组,每组15只,开胸将临时起搏电极缝于右房,实验组以350次/分的频率进行快速心房起搏,每天8 h,连续7 d;于起搏第1,3,7 d测试静息心率、固有心率及校正的窦房结恢复时间(CSNRT),并于实验第7天处死动物,取出窦房结组织,应用逆转录-聚合酶链式反应技术测定HCN4及RyR2 mRNA表达情况。结果经快速心房起搏后7 d,实验组静息心率、固有心率较对照组明显减慢(219.71±3.59次/分vs 272.14±9.44次/分,202.00±4.76次/分vs 224.57±4.50次/分,P均<0.05);CSNRT较对照组明显延长(96.00±3.56 ms vs 73.43±4.62 ms,P<0.05);HCN4及RyR2 mRNA表达明显减弱(0.37±0.04 vs 0.65±0.05,0.49±0.09 vs 0.84±0.06,P均<0.05)。结论快速房性心律失常可导致窦房结功能障碍,其可能的发病机制是HCN4及RyR2表达的减弱。