title: Evidence that two distinct crypt cell types secrete chloride and potassium in human colon.
abstract: BACKGROUND
  Human colon may secrete substantial amounts of water secondary to chloride (Cl(-)) and/or potassium (K(+)) secretion in a variety of diarrhoeal diseases. Ion secretion occurs via Cl(-) and K(+) channels, which are generally assumed to be co-located in the colonocyte apical membrane, although their exact cellular sites remain unclear.
  
  
  OBJECTIVE
  To investigate the location of apical Cl(-) (CFTR) and apical K(+) (large conductance; BK) channels within human colonic epithelium.
  
  
  METHODS
  Whole-cell patch clamp recordings were obtained from intact human colonic crypts. Specific blockers of K(+) channels and CFTR identified different types of K(+) channel and CFTR under resting conditions and after stimulating intracellular cAMP with forskolin. The BK channel β3-subunit was localised by immunostaining.
  
  
  RESULTS
  Two types of crypt cells were identified. One (73% of cells) had whole-cell currents dominated by intermediate conductance (IK) K(+) channels under resting conditions, which developed large CFTR-mediated currents in response to increasing intracellular cAMP. The other (27% of cells) had resting currents dominated by BK channels inhibited by the BK channel blocker penitrem A, but insensitive to both forskolin and the IK channel blocker clotrimazole. Immunostaining showed co-localisation of the BK channel β3-subunit and the goblet cell marker, MUC2.
  
  
  CONCLUSIONS
  In human colon, Cl(-) secretion originates from the dominant population of colonocytes expressing apical CFTR, whereas K(+) secretion is derived from a smaller population of goblet cells expressing apical BK channels. These findings provide new insights into the pathophysiology of secretory diarrhoea and should be taken into account during the development of anti-diarrhoeal drugs.
authors.affiliation: Institute of Systems and Membrane Biology, University of Leeds, , Leeds, West Yorkshire, UK.
authors.forename: John
authors.initials: J
authors.lastname: Linley
authors.forename: Arun
authors.initials: A
authors.lastname: Loganathan
authors.forename: Shashikala
authors.initials: S
authors.lastname: Kopanati
authors.forename: Geoffrey I
authors.initials: GI
authors.lastname: Sandle
authors.forename: Malcolm
authors.initials: M
authors.lastname: Hunter
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D018118:Chloride Channels / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D003106:Colon / Q000166:cytology / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D020397:Goblet Cells / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C505032:CFTR protein, human; D018118:Chloride Channels; D002712:Chlorides; D051036:Large-Conductance Calcium-Activated Potassium Channels; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D011188:Potassium
keywords: BASIC SCIENCES; COLORECTAL PHYSIOLOGY; DIARRHOEA; INTESTINAL ION TRANSPORT; ION CHANNELS