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 transp orting activities simultaneously, of which more than one is increased follo wing activation with a single agonist. These separate activities can be qua ntified 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 wi th those from transgenic animals this has been achieved for electrogenic io n 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 an d cystic fibrosis (CF) mice. 3 Using amiloride it is shown that CF colons show increased electrogenic so dium absorption compared to wild type tissues. CF mice had elevated plasma aldosterone, which may be responsible for part or all of the increased sodi um absorbtion in CF colons. 4 The derived values for electrogenic chloride secretion and for electrogen ic potassium secretion were increased by 13 and 3 fold respectively by fors kolin, 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 s ecretion. However, use of bicarbonate-free solutions and acetazolamide redu ced the frusemide-resistant current, suggesting that electrogenic bicarbona te secretion accounts for the frusemide-resistant current. 6 It is argued that the use of tissues from transgenic animals is an import ant adjunct to pharmacological analysis, especially where effects in tissue s result in the activation of more than one sort of response.