title: Potassium secretion in rat distal colon during dietary potassium loading: role of pH regulated apical potassium channels.
abstract: BACKGROUND
  Chronic dietary K+ loading increases the abundance of large conductance (210 pS) apical K+ channels in surface cells of rat distal colon, resulting in enhanced K+ secretion in this epithelium. However, the factors involved in the regulation of these K+ channels are at present unclear.
  
  
  OBJECTIVE
  To evaluate the effect of dietary K+ loading on intracellular pH and its relation to large conductance apical K+ channel activity in surface cells of rat distal colon.
  
  
  RESULTS
  As assessed by fluorescent imaging, intracellular pH was higher in K+ loaded animals (7.48 (0.09)) than in controls (7.07 (0.04); p<0.01) when surface cells were bathed in NaCl solution, and a similar difference in intracellular pH was observed when cells were bathed in Na2SO4 solution (7.67 (0.09) and 6.92 (0.05) respectively; p<0.001). Ethylisopropylamiloride (EIPA; an inhibitor of Na+-H+ exchange; 1 microM) decreased intracellular pH when surface cells from K+ loaded animals were bathed in either solution, although the decrease was greater when the solution contained NaCl (DeltapH 0.50 (0.03)) rather than Na2SO4 (DeltapH 0. 18 (0.02); p<0.05). In contrast, EIPA had no effect in cells from control animals. As assessed by patch clamp recording techniques, the activity of large conductance K+ channels in excised inside-out membrane patches from distal colonic surface cells of K+ loaded animals increased twofold when the bath pH was raised from 7.40 to 7. 60. As assessed by cell attached patches in distal colonic surface cells from K+ loaded animals, the addition of 1 M EIPA decreased K+ channel activity by 50%, consistent with reversal of Na+-H+ exchange mediated intracellular alkalinisation.
  
  
  CONCLUSIONS
  Intracellular alkalinisation stimulates pH sensitive large conductance apical K+ channels in rat distal colonic surface cells as part of the K+ secretory response to chronic dietary K+ loading. Intracellular alkalinisation seems to reflect an increase in EIPA sensitive Na+-H+ exchange, which may be a manifestation of the secondary hyperaldosteronism associated with this model of colonic K+ adaptation.
authors.affiliation: Molecular Medicine Unit, St James's University Hospital, Leeds, UK.
authors.forename: G I
authors.initials: GI
authors.lastname: Sandle
authors.forename: I
authors.initials: I
authors.lastname: Butterfield
mesh_terms: D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D018929:Cell Culture Techniques; D003106:Colon / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D008297:Male; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D017419:Potassium, Dietary / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors
chemical_list: D015221:Potassium Channels; D017419:Potassium, Dietary; D017923:Sodium-Hydrogen Exchangers; D000584:Amiloride; D011188:Potassium; C039614:ethylisopropylamiloride