Time-dependent stimulation by aldosterone of blocker-sensitive ENaCs in A6 epithelia

• Published in: American Journal of Physiology: Cell Physiology 1998-04, Vol.274 (4), p.C947-C957
• Main Authors: Helman, Sandy I, Liu, Xuehong, Baldwin, Kieron, Blazer-Yost, Bonnie L, Els, Willem J
• Format: Article
• Language: English
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.1998.274.4.c947

1  Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801; 2  Department of Biology, Indiana University-Purdue University at Indianapolis and Veterans Affairs Medical Center, Indianapolis, Indiana 46202; and 3  Department of Anatomy and Cell Biology, University of Cape Town Medical School, Cape Town, South Africa To study and define the early time-dependent response ( 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 ( i Na ) channel open probability ( P o ), and channel density ( N T ) under transient conditions of transport as measured by macroscopic short-circuit currents ( I sc ). In three groups of experiments in which spontaneous baseline rates of transport averaged 1.06, 5.40, and 15.14 µA/cm 2 , stimulation of transport occurred due to increase of blocker-sensitive channels. N T varied linearly over a 70-fold range of transport (0.5-35 µA/cm 2 ). Relatively small and slow time-dependent but aldosterone-independent decreases of P o occurred during control (10-20% over 2 h) and aldosterone experimental periods (10-30% over 6 h). When the P o of control and aldosterone-treated tissues was examined over the 70-fold extended range of Na + transport, P o was observed to vary inversely with I sc , falling from ~0.5 to ~0.15 at the highest rates of Na + transport or ~25% per 3-fold increase of transport. Because decreases of P o 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 N T . electrophysiology; epithelial sodium channels; tissue culture; cortical collecting ducts; kidney; noise analysis; amiloride