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

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

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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 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 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 ?mol/L). In 71.4% of DiI labeled DRG neurons (n = 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 CsCl. In neurons expressing Ih 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 Ih current was potentiated by 8-Br-cAMP, which had no effect on the Ih current of DiI labeled NG neurons. Immunohistochemistry 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, respectively.CONCLUSION: HCNs differentially regulate the excitability of vagal and spinal afferent of murine small intestine.

Hyperpolarization-activated cyclic nucleotide-gated cationVagal afferentSpinal afferentGastrointestinal tractCsCl

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

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Department of Physiology, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China

Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, United Kingdom

Supported by Science and Technology Commission of Shanghai MunicipalityEducational Commission of Shanghai Municipality

10ZR141730010ZZ69

2012

10.3748/wjg.v18.i6.522

世界胃肠病学杂志(英文版)
太原消化病研治中心

世界胃肠病学杂志(英文版)

SCI
影响因子：1.001
ISSN：1007-9327
年,卷(期)：2012.18(6)
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