title: Ca2+ sensitivity of the maxi chloride channel in interstitial cells of Cajal.
abstract: BACKGROUND
  Interstitial cells of Cajal (ICC) associated with the myenteric plexus of the small intestine express maxi chloride channels. Our aim was to investigate whether or not these channels would be activated by increases in intracellular Ca(2+) , as that would strengthen evidence for their potential role in ICC pacemaking. A further aim was to examine whether inwardly and outwardly rectifying maxi chloride currents signify different channels.
  
  
  METHODS
  We used Fluo-4 AM Ca(2+) imaging and patch clamp electrophysiology (cell-attached and inside-out) on isolated ICC in short term culture.
  
  
  RESULTS
  Increasing intracellular Ca(2+) by three functionally distinct mechanisms (blocking sarcoplasmic reticulum Ca(2+) refilling, creating membrane Ca(2+) pores and a solution designed to block plasmalemmal Ca(2+) extrusion) was followed by inwardly rectifying maxi chloride channel activation assessed in the cell-attached configuration. Furthermore, in the inside-out configuration, increased outwardly rectifying maxi-chloride channel activity followed an increase in Ca(2+) to 2 mmol L(-1) at the cytoplasmic face of the channel.
  
  
  CONCLUSIONS
  Increase in intracellular Ca(2+) will activate the maxi chloride channels. Maxi chloride currents are inwardly rectifying in the cell-attached patch clamp configuration under physiological conditions and are outwardly rectifying in the inside-out configuration. The same channel is responsible for both currents. Ca(2+) does not appear to regulate the rectification.
authors.affiliation: Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada.
authors.forename: G W J
authors.initials: GW
authors.lastname: Wright
authors.forename: S P
authors.initials: SP
authors.lastname: Parsons
authors.forename: J D
authors.initials: JD
authors.lastname: Huizinga
mesh_terms: D000818:Animals; D000075369:Anoctamin-1; D002118:Calcium / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D018118:Chloride Channels / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D055724:Electrophysiological Phenomena; D005456:Fluorescent Dyes; D007211:Indoles / Q000494:pharmacology; D056885:Interstitial Cells of Cajal / Q000187:drug effects / Q000378:metabolism*; D015640:Ion Channel Gating / Q000187:drug effects; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D007811:Lanthanum / Q000494:pharmacology; D051379:Mice; D059906:Neuroimaging; D018408:Patch-Clamp Techniques; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism
chemical_list: C531181:ANO1 protein, mouse; D000075369:Anoctamin-1; D018118:Chloride Channels; D005456:Fluorescent Dyes; D007211:Indoles; D007476:Ionophores; D015759:Ionomycin; D007811:Lanthanum; D002118:Calcium; C000543:cyclopiazonic acid