Sulphonylurea receptors differently modulate ICC pacemaker Ca2+ activity and smooth muscle contractility

Shinsuke Nakayama, Susumu Ohya, Hong Nian Liu, Toshiya Watanabe, Shinji Furuzono, Jing Wang, Yuji Nishizawa, Masahiro Aoyama, Naruhiko Murase, Tatsuaki Matsubara, Yasushi Ito, Yuji Imaizumi, Shunichi Kajioka

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Abstract

Appropriate gastrointestinal motility is essential to properly control the body energy level. Intracellular Ca2+ ([Ca2+]i) oscillations in interstitial cells of Cajal (ICCs; identified with c-Kit immunoreactivity) are considered to be the primary mechanism for the pacemaker activity in gastrointestinal motility. In the present study, RT-PCR examinations revealed predominant expression of the type 1 isoform of sulphonylurea receptors (SUR1) in ICCs of the mouse ileum, but expression of SUR2 was predominant in smooth muscle. In cell clusters prepared from the same tissue, smooth muscle contractility and pacemaker [Ca2+]i activity in ICCs were found to be differentially modulated by KATP channel openers and sulphonylurea compounds, in accordance with the expression of SUR isoforms. 1 μM cromakalim nearly fully suppressed the mechanical activity in smooth muscle, whereas ICC pacemaker [Ca2+]i oscillations persisted. Greater concentrations (∼10 μM) of cromakalim attenuated pacemaker [Ca2+]i oscillations. This effect was not reversed by changing the reversal potential of K+, but was prevented by glibenclamide. Diazoxide at 30 μM terminated ICC pacemaker [Ca2+]i oscillations, but again treatment with high extracellular K+ did not restore them. These results suggest that SUR can modulate pacemaker [Ca2+]i oscillations via voltage-independent mechanism(s), and also that intestinal pacemaking and glucose control are closely associated with SUR.

Original languageEnglish
Pages (from-to)4163-4173
Number of pages11
JournalJournal of Cell Science
Volume118
Issue number18
DOIs
Publication statusPublished - Sep 15 2005
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Nakayama, S., Ohya, S., Liu, H. N., Watanabe, T., Furuzono, S., Wang, J., ... Kajioka, S. (2005). Sulphonylurea receptors differently modulate ICC pacemaker Ca2+ activity and smooth muscle contractility. Journal of Cell Science, 118(18), 4163-4173. https://doi.org/10.1242/jcs.02540