title: Sphingosine and FTY720 modulate pacemaking activity in interstitial cells of Cajal from mouse small intestine.
abstract: Interstitial cells of Cajal (ICCs) are the pacemakers of the gastrointestinal tract, and transient receptor potential melastatin type 7 (TRPM7) and Ca(2+) activated Cl(-) channels (ANO1) are candidate the generators of pacemaker potentials in ICCs. The effects of D-erythro-sphingosine (SPH) and structural analogues of SPH, that is, N,N-dimethyl-Derythro-sphingosine (N,N-DMS), FTY720, and FTY720-P on the pacemaking activities of ICCs were examined using the whole cell patch clamp technique. SPH, N,N-DMS, and FTY720 decreased the amplitudes of pacemaker potentials in ICC clusters, but resting membrane potentials displayed little change. Also, perfusing SPH, N,N-DMS, or FTY720 in the bath reduced both inward and outward TRPM7-like currents in single ICCs, and inhibited ANO1 currents. The another structural analogue of SPH, FTY720-P was ineffective at the pacemaker potentials in ICC clusters and the TRPM7-like currents in single ICCs. Furthermore, FTY720-P had no effect on ANO1. These results suggest that SPH, N,N-DMS, and FTY720 modulate the pacemaker activities of ICCs, and that TRPM7 and ANO1 channels affect intestinal motility.
authors.affiliation: Department of Physiology, Dongguk University College of Medicine, Kyungju, 780-714, Korea.
authors.forename: Joo Hyun
authors.initials: JH
authors.lastname: Nam
authors.forename: Woo Kyung
authors.initials: WK
authors.lastname: Kim
authors.forename: Byung Joo
authors.initials: BJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D001683:Biological Clocks; D018118:Chloride Channels / Q000502:physiology*; D005260:Female; D000068876:Fingolimod Hydrochloride; D005769:Gastrointestinal Motility / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D056885:Interstitial Cells of Cajal / Q000187:drug effects / Q000502:physiology*; D007421:Intestine, Small / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials; D051379:Mice; D008807:Mice, Inbred BALB C; D010755:Organophosphates / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011409:Propylene Glycols / Q000494:pharmacology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D050053:TRPM Cation Channels / Q000187:drug effects / Q000235:genetics / Q000502:physiology*
chemical_list: D018118:Chloride Channels; C525008:FTY 720P; D010755:Organophosphates; D011409:Propylene Glycols; D050053:TRPM Cation Channels; C421903:Trpm7 protein, mouse; D000068876:Fingolimod Hydrochloride; C061800:N,N-dimethylsphingosine; D013110:Sphingosine
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