Factors influencing the electrical potential across the mucosa of rat colon.

1. An investigation has been carried out into various factors which influence the transmucosal potential difference (p.d.) of rat colon in vivo when the p.d. is either high (> 30 mV) or low (< 20 mV).2. The p.d. was uninfluenced by short duration anaesthesia with ether or pentobarbitone. When anaesthesia was prolonged for several hours, p.d. rose steadily. The gradient of p.d. along the descending colon which developed and its elimination by adrenalectomy suggested that the rise was due to increased secretion of adrenal steroids.3. P.d. was increased by Na depletion after a delay of about 18 hr and fell again following Na repletion with a similar time delay. A characteristic gradient of p.d. along the descending colon was seen.4. Both haemorrhage and anoxia caused a rapid fall of p.d. P.d. was restored rapidly to its previous level when anoxia was corrected.5. Vasopressin (I.V.) in low dose was without effect; in high dose it caused a transient fall of p.d. associated with intense vasoconstriction of gut blood vessels.6. The following factors studied were without effect on p.d.: presence of glucose within the lumen; considerable osmotic gradients across the mucosa; variation of luminal pH over the range 5.2-9.8; intravenous administration of acetazolamide, chlorothiazide, frusemide, triamterene, ethacrynic acid or ouabain. Ouabain in the luminal solution also had no effect in all but two rats in which a small fall of p.d. was seen.7. 2,4-dinitrophenol, 10(-2)M, in the lumen caused a small fall of p.d. only if the p.d. was high.8. Experiments were done to determine the effect on p.d. of altering the ionic composition of the luminal solution. When the p.d. was low (< 20 mV) alteration of [Na], [K] or [Cl] produced small absolute changes of the p.d., all of comparable magnitude. The changes could be interpreted as due to diffusion potentials resulting from the ionic gradients across the mucosa. When the p.d. was high (> 30 mV), it showed a striking dependence on the luminal [Na] only, consistent with the presence of a large p.d. due to active Na transport.