CONTROL OF ELECTROGENIC NA+ ABSORPTION IN RAT LATE DISTAL COLON BY NANOMOLAR ALDOSTERONE ADDED INVITRO

It has been possible to obtain in a mammalian epithelium of dietetically and surgically untreated animals a dose response of in vitro-added aldosterone (Aldo, 10(-10) to 10(-5) M) on electrogenic Na+ absorption (J(Na)e).J(Na)e was measured in the Ussing chamber on stripped rat late distal colon 8 h after in vitro addition of Aldo. Submaximal effects were obtained at 3 nM Aldo; after a lag time of 2 h, short-circuit current (I(sc)) increased to a maximum of 234 +/- 15 muA/cm2 and dropped after 0.1 mM amiloride to -18 +/- 3 muA/cm2, resulting in J(Na)e of 9.4 +/- 0.6 mumol.h-1.cm-2. Net Na+ tracer fluxes and I(sc) exhibited parallel time courses, so that electroneutral Na+ transport was not induced in late distal colon by acute Aldo. A plot of J(Na)e vs. Na conductance revealed an electromotive force (E(Na)e) of 126 +/- 1 mV for all Aldo concentrations tested. Kinetic data were as follows: Michaelis constant 1.2 nM, maximal velocity (V(max)) 10.5 mumol.h-1.cm-2, and Hill coefficient 2.1. In contrast to the large effect in late distal colon, 3 nM Aldo caused JeN. of <1 mumol.h-1.cm-2 in early distal colon, proximal colon, and cecum. Antimineralocorticoid sensitivity and E(Na) did not vary with Aldo concentration or time of the experiment, consistent with a unique mechanism during the early and late response up to 8 h, as well as at mineralocorticoid and glucocorticoid Aldo concentrations. Acute Aldo in a range of 0.1-10 nM fully controls J(Na)e between zero and V(max) in late distal colon. Under acute 3 nM Aldo J(Na)e is localized in late distal colon rather than in the entire distal colon as observed at very high Aldo levels.