Hyperpolarization-activated cyclic nucleotide-gated cation channel subtypes differentially modulate the excitability of murine small intestinal afferents  

作　　者：Ying-Ping Wang Bi-Ying Sun Qian Li Li Dong Guo-Hua Zhang David Grundy Wei-Fang Rong 

机构地区：[1]Department of Physiology,Shanghai Jiaotong University School of Medicine,Shanghai 200025,China [2]Department of Biomedical Science,University of Sheffield,Sheffield S10 2TN,United Kingdom

出　　处：《World Journal of Gastroenterology》2012年第6期522-531,共10页世界胃肠病学杂志（英文版）

基　　金：Supported by Science and Technology Commission of Shanghai Municipality,No. 10ZR1417300;Educational Commission of Shanghai Municipality,No. 10ZZ69

摘　　要：AIM： To assess the role of hyperpolarization-activated cyclic nucleotide-gated cation （HCN） channels in regu- lating the excitability of vagal and spinal gut afferents. METHODS： The mechanosensory response of mesen- teric afferent activity was measured in an ex vivo murine jejunum preparation. HCN channel activity was recorded through voltage and current clamp in acutely dissoci- ated 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 evok- ed biphasic increases in the afferent nerve activity, re- flecting 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 re- sponses. The effect of CsCI was mimicked by the more selective HCN blocker ZD7288 （10 ~mol/L）. In 71.4% of DiI labeled DRG neurons （/7 = 20） and 90.9% of DiI labeled NG neurons （n = 10）, an inward current （Ih current） was evoked by hyperpolarization pulses which was fully eliminated by extracellular CsCI. In neurons expressing Ih current, a typical ＂sag＂ was observed upon injection of hyperpolarizing current pulses in cur- rent-clamp recordings. CsCI abolished the sag entirely. In some DiI labeled DRG neurons, the Ih current was potentiated by 8-Br-cAMP, which had no effect on the Ih current of DiI labeled NG neurons. Immunohistochem- istry revealed differential expression of HCN isoforms in vagal and spinal afferents, and HCN2 and HCN3 seemed to be the dominant isoform in DRG and NG, respec- tively.CONCLUSION： HCNs differentially regulate the excit- ability of vagal and spinal afferent of murine small in- testine.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.

关 键 词：Hyperpolarization-activated cyclic nucleo-tide-gated cation Vagal afferent Spinal afferent Gas-trointestinal tract CSCI 

分 类 号：Q73[生物学—分子生物学] S852.12[农业科学—基础兽医学]