title: Sulphonylurea receptors differently modulate ICC pacemaker Ca2+ activity and smooth muscle contractility.
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 K(ATP) channel openers and sulphonylurea compounds, in accordance with the expression of SUR isoforms. 1 microM cromakalim nearly fully suppressed the mechanical activity in smooth muscle, whereas ICC pacemaker [Ca2+]i oscillations persisted. Greater concentrations (approximately 10 microM) 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 muM 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.
authors.affiliation: Department of Cell Physiology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan. h44673a@nucc.cc.nagoya-u.ac.jp
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Nakayama
authors.forename: Susumu
authors.initials: S
authors.lastname: Ohya
authors.forename: Hong-Nian
authors.initials: HN
authors.lastname: Liu
authors.forename: Toshiya
authors.initials: T
authors.lastname: Watanabe
authors.forename: Shinji
authors.initials: S
authors.lastname: Furuzono
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nishizawa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Aoyama
authors.forename: Naruhiko
authors.initials: N
authors.lastname: Murase
authors.forename: Tatsuaki
authors.initials: T
authors.lastname: Matsubara
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ito
authors.forename: Yuji
authors.initials: Y
authors.lastname: Imaizumi
authors.forename: Shunichi
authors.initials: S
authors.lastname: Kajioka
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D015220:Calcium Channels / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D019806:Cromakalim / Q000494:pharmacology; D003981:Diazoxide / Q000494:pharmacology; D007082:Ileum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D007150:Immunohistochemistry; D054086:KATP Channels; D051379:Mice; D008807:Mice, Inbred BALB C; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying / Q000096:biosynthesis; D011955:Receptors, Drug; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel
chemical_list: D018528:ATP-Binding Cassette Transporters; D002118:Calcium; D015220:Calcium Channels; D019806:Cromakalim; D003981:Diazoxide; D054086:KATP Channels; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel; C577508:Abcc8 protein, mouse; C092520:uK-ATP-1 potassium channel