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

World Journal of Gastroenterology : WJG
Ying-Ping WangWei-Fang Rong

Abstract

To assess the role of hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels in regulating the excitability of vagal and spinal gut afferents. 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. 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 CsC...Continue Reading

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