Si. Helman et al., TIME-DEPENDENT STIMULATION BY ALDOSTERONE OF BLOCKER-SENSITIVE ENACS IN A6 EPITHELIA, American journal of physiology. Cell physiology, 43(4), 1998, pp. 947-957
To study and define the early time dependent response (less than or eq
ual to 6 h) of blocker-sensitive epithelial Na+ channels (ENaCs) to st
imulation of Na+ transport by aldosterone, we used a new modified meth
od of blocker-induced noise analysis to determine the changes of singl
e-channel current (i(Na)) channel open probability (P-o), and channel
density (N-T) under transient conditions of transport as measured by m
acroscopic short-circuit currents (I-sc). In three groups of experimen
ts in which spontaneous baseline rates of transport averaged 1.06, 5.4
0, and 15.14 mu A/cm(2), stimulation of transport occurred due to incr
ease of blocker-sensitive channels. N-T varied linearly over a 70-fold
range of transport (0.5-35 mu A/cm(2)). Relatively small and slow tim
e-dependent but aldosterone-independent decreases of P-o occurred duri
ng 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 wa
s observed to vary inversely with I-sc, falling from similar to 0.5 to
similar to 0.15 at the highest rates of Na+ transport or similar to 2
5% 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 i
n A6 epithelia is due exclusively to increase of apical membrane N-T.