Time-dependent stimulation by aldosterone of blocker-sensitive ENaCs in A6 epithelia.
To study and define the early time-dependent response (< or = 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 microA/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 microA/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 approximately 0.5 to approximately 0.15 at the highest rates of Na+ transport or approximately 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.
Helman
S I
SI
Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign 61801, USA.
Liu
X
X
Baldwin
K
K
Blazer-Yost
B L
BL
Els
W J
WJ
D000450:Aldosterone / Q000494:pharmacology*; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D004553:Electric Conductivity; D004847:Epithelial Cells / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D013997:Time Factors
D015222:Sodium Channels; C058206:6-chloro-3,5-diaminopyrazine-3-carboxamide; D000450:Aldosterone; D000584:Amiloride