AJP - Cell Physiology, Vol 254, Issue 2 C297-C303, Copyright © 1988 by American Physiological Society
Complex response of epithelial cells to inhibition of Na+ transport by amiloride
R. S. Fisher and J. W. Lockard
Department of Nephrology, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
When toad urinary bladder or frog skin epithelia are treated with
amiloride, short-circuit current (Isc), which represents the net active
transepithelial Na+ transport rate from the apical to basolateral surface,
decreases rapidly (2-5 s) to approximately 15-20% of control values and
then slowly, over several minutes, continues falling toward zero. The
contribution of this second phase of the decline is dependent on the
transporting condition of the tissue before administration of amiloride.
Attenuation of the second phase was observed if tissues were subjected to a
period of transport inhibition. Tissues preincubated in 0 Na+ Ringer
solution on the apical surface were returned to control Na+ Ringer, which
caused an approximately 25% increase of Isc above control values. Immediate
reapplication of amiloride caused Isc to decrease more rapidly than the
previous exposure to values near zero, substantially reducing or
eliminating the secondary slow decline. After long-term reincubation of
tissues in control, 100 mM Na+ solution, another treatment with amiloride
indicated that the magnitude of the secondary decline increased in frog
skin but not in urinary bladder epithelia. We conclude that the effect of
amiloride is complex and may cause additional effects besides simply
blocking entry of Na+ into the apical membrane channel, and we suggest that
regulatory mechanisms may be invoked in response to transport inhibition.
