Oxytocin hyperpolarizes cultured duodenum myenteric intrinsic primary afferent neurons by opening BK Ca channels through IP 3 pathway

Tongtong Che, Hui Sun, Jingxin Li, Xiao Yu, Dexiao Zhu, Bing Xue, Kejing Liu, Min Zhang, Wolfgang Kunze, Chuanyong Liu

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


Oxytocin (OT) is clinically important in gut motility and constitutively reduces duodenum contractility. Intrinsic primary afferent neurons (IPANs), whose physiological classification is as AH cells, are the 1st neurons of the peristaltic reflex pathway. Weset out to investigate if this inhibitory effect is mediated by IPANs and to identify the ion channel(s) and intracellular signal transduction pathway that are involved in this effect. Myenteric neurons were isolated from the longitudinal muscle myenteric plexus (LMMP) preparation of rat duodenum and cultured for 16-24 h before electrophysiological recording in whole cell mode and AH cells identified by their electrophysiological characteristics. The cytoplasmic Ca 2+ concentration ([Ca 2+] i) of isolated neurons was measured using calcium imaging. The concentration of IP 3 in the LMMP and the OT secreted from the LMMP were measured using ELISA. The oxytocin receptor (OTR) and large-conductance calcium-activated potassium (BK Ca) channels, as well as the expression of OT and the IPAN marker calbindin 28 K, on the myenteric plexus neurons were localized using double-immunostaining techniques. We found that administration of OT (10 -7 to 10 -5 M) dose dependently hyperpolarized the resting membrane potential and increased the total outward current. The OTR antagonist atosiban or the BK Ca channel blocker iberiotoxin (IbTX) blocked the effects of OT suggesting that the increased outward current resulted from BK Ca channel opening. OTR and the BK Ca α subunit were co-expressed on a subset of myenteric neurons at the LMMP. NS1619 (10 -5 M, a BK Cachannel activator) increased the outward current similar to the effect of OT. OT administration also increased [Ca 2+] i and the OT-evoked outward current was significantly attenuated by thapsigargin (10 -6 M) or CdCl 2. The effect of OT on the BK Cacurrent was also blocked by pre-treatment with the IP 3 receptor antagonist 2-APB (10 -4 M) or the PLC inhibitor U73122 (10 -5 M). OT (10 -6 M) also increased the IP 3 concentration within the LMMP. Both of the spontaneous and KCl-induced secretion of OT was enhanced by atosiban. Most of OT-immunoreactive cells are also immunoreactive for calbindin 28 K. In summary, we concluded that OT hyperpolarized myenteric IPANs by activating BK Ca channels via the OTR-PLC-IP 3-Ca 2+ signal pathway. OT might modulate IPANs mediated ENS reflex by an autocrine and negative feedback manner.

Original languageEnglish (US)
Pages (from-to)516-525
Number of pages10
JournalJournal of neurochemistry
Issue number4
StatePublished - May 2012
Externally publishedYes


  • AH cell
  • BK channel
  • IP
  • Oxytocin
  • PLC

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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