AJP - Cell Physiology, Vol 258, Issue 6 C1150-C1158, Copyright © 1990 by American Physiological Society
Furosemide blocks basolateral membrane Cl- permeability in gallbladder epithelium
J. S. Stoddard, G. A. Altenberg, M. L. Ferguson and L. Reuss
Department of Physiology and Biophysics, University of Texas Medical Branch, Galveston 77550.
In Necturus gallbladders bathed in a NaCl Ringer solution buffered with 10
mM HCO3(-)-1% CO2, furosemide (added to the serosal solution) caused a
concentration-dependent hyperpolarization of both cell membranes that was
slow and reversible. At 10(-3) M furosemide, the basolateral membrane
voltage (Vcs) increased significantly from -71 +/- 3 to -85 +/- 3 mV, the
depolarization of Vcs elicited by a 10-fold rise in serosal [K+] increased
from 34 +/- 4 to 50 +/- 1 mV, the depolarization elicited by lowering
serosal [Cl-] from 98 to 8.1 mM was reduced from 15 +/- 1 to 1 +/- 1 mV,
and the depolarization in response to lowering serosal [HCO3-] from 10 to 1
mM was reduced from 13 +/- 1 to 5 +/- 0.4 mV. Furosemide could in principle
decrease the basolateral membrane Cl- conductance (Gcl), increase the
basolateral membrane K+ conductance, or have a combined effect. To
distinguish among these possibilities, we estimated the resistance of the
basolateral membrane (Rb) by means of two-point intraepithelial cable
analysis experiments. Furosemide increased Rb by 22%, which indicates that
furosemide reduces basolateral membrane Gcl. The effect cannot be
attributed to inhibition of apical membrane anion exchange by serosal
addition of furosemide, because base secretion from cells to lumen is
unchanged. We conclude that furosemide blocks reversibly basolateral
membrane electrodiffusive Cl- permeability. A concomitant stimulation of
basolateral membrane electrodiffusive K+ permeability is also possible.
