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The model of sodium and chloride transport proposed for the colon is based on studies performed in the distal segment and tacitly assumes that ion transport is similar throughout the colon. In rat distal colon, neutral sodium-chloride absorption accounts for the major fraction of overall sodium absorption and aldosterone stimulates electrogenic, amiloride-sensitive sodium absorption. Since we have demonstrated qualitative differences in potassium transport in proximal and distal segments of rat colon, unidirectional 22Na and 'Cl fluxes were performed under shortcircuit conditions across isolated proximal colon of control and sodium-depleted rats with secondary hyperaldosteronism. In the control group, net sodium absorption (JN:) (7.4±0.5 Ateq/h * cm2) was greater than I,, (1.4±0.1 lueq/h cm2), and JPt was 0 in Ringer solution. Residual flux (J) was -5.2±0.5 teq/h cm2 consistent with hydrogen ion secretion suggesting that neutral sodium absorption may represent sodium-hydrogen exchange. 1 mM mucosal amiloride, which inhibits sodium-hydrogen exchange in other epithelia, produced comparable decreases in J" and JR (4.1±0.6 and 3.2±0.6 ;&eq/h * cm2, respectively) without a parallel fall in I,<. Sodium depletion stimulated JN, JA, and I., by 7.0±1.4, 6.3±1.9, and 0.8±0.2 ;eq/h cm2, respectively, and 1 mM amiloride markedly inhibited JN' and J by 6.0±1.1 and 4.0±1.6 ,ueq/h * cm2, respectively, with only a minimal reduction in I4.. Conclusions: the predominant neutral sodium-absorptive mechanism in proximal colon is sodium-hydrogen exchange. Sodium depletion stimulates electroneutral chloride-dependent sodium absorption (most likely as a result of increasing sodium-hydrogen and chloride-bicarbonate exchanges), not electrogenic chloride-independent sodium transport. The model of ion transport in the proximal colon is distinct from that of the distal colon.

Studies were performed, using a synthetic glucocorticoid, RU 28362, that has negligible binding to aldosterone receptors, to examine whether the effect of glucocorticoids on the electrical properties of rat distal colon involves a specific mechanism or crossover binding to aldosterone receptor sites. Compared with control, RU 28362, in a dose of 70 micrograms.100 g body wt-1.day-1, increased transepithelial potential differences (VT) twofold and the equivalent short-circuit current (ISC) threefold; epithelial resistance (RT) was reduced 25%. These changes were qualitatively similar to, but less than, the changes induced by the same dose of aldosterone. The effects of dexamethasone in the same dose were indistinguishable from the changes caused by aldosterone. The results of cell-impalement studies corresponded to whole epithelial changes; RU 28362 induced a small increase in basolateral potential difference, from -43 +/- 2 to -45 +/- 1 mV, and a fall in apical potential difference, from 40 +/- 2 to 36 +/- 1 mV, but these effects on cell membrane voltage were less than caused by either aldosterone or dexamethasone. In contrast to the marked inhibitory action of amiloride to reduce VT in aldosterone- and dexamethasone-treated animals, this sodium channel blocker had no effect on VT in RU 28362-treated animals. Similarly, while spironolactone caused marked inhibition of the changes in VT, RT, and ISC induced by aldosterone, the inhibitory action on tissue from RU 28362-treated animals was slight or absent. These results suggest that glucocorticoids have a specific aldosterone receptor-independent action on the electrical properties of the large intestine.

Increased dietary potassium ("potassium loading") induces several adaptive changes in colonic function, including increased potential-dependent potassium secretion, active potassium secretion, and Na-K-ATPase activity, but does not alter net sodium absorption in vivo. To establish whether potassium loading stimulates active sodium transport, unidirectional, net sodium, and chloride fluxes were determined under voltage-clamp conditions across isolated rat distal colonic mucosa. In normal animals net sodium flux (JNanet), net chloride flux (JClnet) and short-circuit current (Isc) were 6.1 +/- 1.1, 8.4 +/- 1.0, and 0.7 +/- 0.1 mu eq X h-1. cm-2, respectively; potassium loading significantly increased JNanet and Isc by 4.9 +/- 1.4 and 3.5 +/- 0.7 mu eq X h-1 X cm-2, respectively, without changing JClnet. Amiloride (0.1 mM) inhibited the increases in JNanet and Isc produced by potassium loading. In Cl-free Ringer solution in normal animals JNanet was reduced to 0.6 +/- 0.3 mu eq X h-1 X cm-2. Potassium loading produced identical increases in JNanet and Isc, which were also completely inhibited by 0.1 mM amiloride. These studies establish that potassium loading induces amiloride-sensitive electrogenic sodium absorption without affecting electroneutral sodium-chloride absorption.