title: Involvement of Na(+)-leak channel in substance P-induced depolarization of pacemaking activity in interstitial cells of Cajal.
abstract: Interstitial cells of Cajal (ICCs) are the pacemaking cells in the gastrointestinal muscles that generate the rhythmic oscillations in membrane potential known as slow waves. ICCs also mediate or transduce inputs from the enteric nervous system. Substance P (SubP) is a member of the family of mammalian tachykinin peptides that are predominantly released by enteric neurons. This study assessed the relationship of Na(+)-leak channel (NALCN) in the SubP-induced depolarization in pacemaking activity in the gastrointestinal tract. The patch-clamp technique for whole-cell recording was used in cultured cluster and single ICCs. Electrophysiological and pharmacological properties of SubP in ICC pacemaking activity were similar to those of NALCN. Reverse-transcription polymerase chain reaction, Western blotting, and immunohistochemistry all showed abundant and localized expression of NALCN messenger RNA and protein in mouse small intestine. NALCN is involved in the SubP-induced depolarization of intestinal pacemaking activity. The protein is a potential target for pharmacological treatment of motor disorders of the gut.
authors.affiliation: Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan, Korea.
authors.forename: Byung Joo
authors.initials: BJ
authors.lastname: Kim
authors.forename: In Youb
authors.initials: IY
authors.lastname: Chang
authors.forename: Seok
authors.initials: S
authors.lastname: Choi
authors.forename: Jae Yeoul
authors.initials: JY
authors.lastname: Jun
authors.forename: Ju-Hong
authors.initials: JH
authors.lastname: Jeon
authors.forename: Wen-Xie
authors.initials: WX
authors.lastname: Xu
authors.forename: Young Kyu
authors.initials: YK
authors.lastname: Kwon
authors.forename: Dejian
authors.initials: D
authors.lastname: Ren
authors.forename: Insuk
authors.initials: I
authors.lastname: So
mesh_terms: D000818:Animals; D001683:Biological Clocks; D015153:Blotting, Western; D002478:Cells, Cultured; D055724:Electrophysiological Phenomena; D017615:Enteric Nervous System / Q000378:metabolism / Q000502:physiology; D005769:Gastrointestinal Motility; D007150:Immunohistochemistry; D056885:Interstitial Cells of Cajal / Q000378:metabolism / Q000502:physiology*; D007421:Intestine, Small / Q000378:metabolism / Q000502:physiology; D007473:Ion Channels / Q000378:metabolism*; D008564:Membrane Potentials; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015222:Sodium Channels / Q000378:metabolism* / Q000502:physiology; D013373:Substance P / Q000494:pharmacology*
chemical_list: D007473:Ion Channels; D008565:Membrane Proteins; C519922:NALCN protein, mouse; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D012333:RNA, Messenger; D015222:Sodium Channels; D013373:Substance P