Formal analysis of electrogenic sodium, potassium, chloride and bicarbonate transport in mouse colon epithelium.
1. The mammalian colonic epithelium carries out a number of different transporting activities simultaneously, of which more than one is increased following activation with a single agonist. These separate activities can be quantified by solving a set of equations describing these activities, provided some of the dependent variables can be eliminated. Using variations in the experimental conditions, blocking drugs and comparing wild type tissues with those from transgenic animals this has been achieved for electrogenic ion transporting activity of the mouse colon. 2. Basal activity and that following activation with forskolin was measured by short circuit current in isolated mouse colonic epithelia from normal and cystic fibrosis (CF) mice. 3. Using amiloride it is shown that CF colons show increased electrogenic sodium absorption compared to wild type tissues. CF mice had elevated plasma aldosterone, which may be responsible for part or all of the increased sodium absorbtion in CF colons. 4. The derived values for electrogenic chloride secretion and for electrogenic potassium secretion were increased by 13 and 3 fold respectively by forskolin, compared to basal state values for these processes. 5. The loop diuretic, frusemide, completely inhibited electrogenic potassium secretion, but apparently only partially inhibited electrogenic chloride secretion. However, use of bicarbonate-free solutions and acetazolamide reduced the frusemide-resistant current, suggesting that electrogenic bicarbonate secretion accounts for the frusemide-resistant current. 6. It is argued that the use of tissues from transgenic animals is an important adjunct to pharmacological analysis, especially where effects in tissues result in the activation of more than one sort of response.
Department of Pharmacology, University of Cambridge.
A W
AW
Cuthbert
M E
ME
Hickman
L J
LJ
MacVinish
D000086:Acetazolamide / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000493:pharmacokinetics; D001692:Biological Transport / Q000187:drug effects; D002712:Chlorides / Q000493:pharmacokinetics; D005576:Colforsin / Q000494:pharmacology; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D003550:Cystic Fibrosis / Q000378:metabolism / Q000503:physiopathology; D004232:Diuretics / Q000494:pharmacology; D004594:Electrophysiology; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D005665:Furosemide / Q000494:pharmacology; D066298:In Vitro Techniques; D007287:Inorganic Chemicals / Q000493:pharmacokinetics*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D018181:Mice, Inbred CFTR; D008962:Models, Theoretical; D011188:Potassium / Q000493:pharmacokinetics; D012964:Sodium / Q000493:pharmacokinetics
D001639:Bicarbonates; D002712:Chlorides; D004232:Diuretics; D007287:Inorganic Chemicals; D005576:Colforsin; D000584:Amiloride; D005665:Furosemide; D012964:Sodium; D000086:Acetazolamide; D011188:Potassium