Time-dependent stimulation by aldosterone of blocker-sensitive ENaCs in A6 epithelia
Helman, S.I.; Liu, X.; Baldwin, K.; Blazer-Yost, B.L.; Els, W.J.
American Journal of Physiology 274(4): C947-C957
1998
ISSN/ISBN: 0002-9513 PMID: 9575791 Document Number: 489933
To study and define the early time-dependent response (ltoreq 6 h) of blocker-sensitive epithelial Na+ channels (ENaCs) to stimulation of Na+ transport by aldosterone, we used a new modified method of blocker-induced noise analysis to determine the changes of single-channel current (iNa) channel open probability (Po), and channel density (NT) under transient conditions of transport as measured by macroscopic short-circuit currents (Isc). In three groups of experiments in which spontaneous baseline rates of transport averaged 1.06, 5.40, and 15.14 muA/cm2, stimulation of transport occurred due to increase of blocker-sensitive channels. NT varied linearly over a 70-fold range of transport (0.5-35 muA/cm2). Relatively small and slow time-dependent but aldosterone-independent decreases of Po occurred during control (10-20% over 2 h) and aldosterone experimental periods (10-30% over 6 h). When the Po of control and aldosterone-treated tissues was examined over the 70-fold extended range of Na+ transport, Po was observed to vary inversely with Isc, falling from apprx 0.5 to apprx 0.15 at the highest rates of Na+ transport or apprx 25% per 3-fold increase of transport. Because decreases of Po from any source cannot explain stimulation of transport by aldosterone, it is concluded that the early time-dependent stimulation of Na+ transport in A6 epithelia is due exclusively to increase of apical membrane NT.