title: Involvement of mitochondrial Na+-Ca2+ exchange in intestinal pacemaking activity.
abstract: OBJECTIVE
  Interstitial cells of Cajal (ICCs) are the pacemaker cells that generate slow waves in the gastrointestinal (GI) tract. We have aimed to investigate the involvement of mitochondrial Na+-Ca2+ exchange in intestinal pacemaking activity in cultured interstitial cells of Cajal.
  
  
  METHODS
  Enzymatic digestions were used to dissociate ICCs from the small intestine of a mouse. The whole-cell patch-clamp configuration was used to record membrane currents (voltage clamp) and potentials (current clamp) from cultured ICCs.
  
  
  RESULTS
  Clonazepam and CGP37157 inhibited the pacemaking activity of ICCs in a dose-dependent manner. Clonazepam from 20 to 60 micromol/L and CGP37157 from 10 to 30 micromol/L effectively inhibited Ca2+ efflux from mitochondria in pacemaking activity of ICCs. The IC50s of clonazepam and CGP37157 were 37.1 and 18.2 micromol/L, respectively. The addition of 20 micromol/L NiCl2 to the internal solution caused a "wax and wane" phenomenon of pacemaking activity of ICCs.
  
  
  CONCLUSIONS
  These results suggest that mitochondrial Na+-Ca2+ exchange has an important role in intestinal pacemaking activity.
authors.affiliation: Department of Physiology and Biophysics, College of Medicine, Seoul National University, 28 Yongon-Dong, Chongno-Gu, Seoul 110-799, Republic of Korea.
authors.forename: Byung Joo
authors.initials: BJ
authors.lastname: Kim
authors.forename: Jae Yeoul
authors.initials: JY
authors.lastname: Jun
authors.forename: Insuk
authors.initials: I
authors.lastname: So
authors.forename: Ki Whan
authors.initials: KW
authors.lastname: Kim
mesh_terms: D000818:Animals; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology*; D002998:Clonazepam / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009532:Nickel / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013841:Thiazepines / Q000494:pharmacology
chemical_list: D019831:Sodium-Calcium Exchanger; D013841:Thiazepines; D002998:Clonazepam; C079032:CGP 37157; D009532:Nickel