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University of Texas Medical School at Houston, Houston, Texas 77030
In tubules from
the terminal segment of the inner medullary collecting duct (tIMCD)
from rats with chronic metabolic acidosis, our laboratory has shown
that bicarbonate absorption
(JtCO2) is inhibited by removal of K+ from
the luminal fluid or by the addition of Sch-28080 to the perfusate. The
present study asked whether total and/or Sch-28080-sensitive JtCO2 is
regulated by changes in systemic
K+ homeostasis. Rat tIMCD tubules
were perfused in vitro in symmetrical, HCO
3/CO2-buffered
solutions containing 10 mM KCl + 6 mM
NH4Cl. Total and
Sch-28080-sensitive
JtCO2 were
measured in rats with varying K+
intake. In K+-replete rats,
baseline JtCO2
was 2.1 ± 0.3 pmol · mm1 · min1
(n = 6). In rats fed a
K+-deficient diet for 3 days,
JtCO2 was 5.4 ± 0.7 pmol · mm1 · min1
(n = 16, P < 0.05). To determine the
mechanism for the increase in HCO3
absorption observed with K+
restriction, the Sch-28080-sensitive component of
JtCO2 was
measured in each treatment group. Following the addition of Sch-28080
(10 µM) to the perfusate, a 40% reduction in
JtCO2 was
observed in K+-restricted rats.
JtCO2 was not
reduced following the addition of Sch-28080 in rats with normal
K+ intake. Because
Sch-28080-sensitive
JtCO2 was
increased in K+-restricted rats,
Sch-28080-sensitive
JtCO2 was studied
further in tIMCD tubules from rats in this treatment group. In
K+-restricted rats,
JtCO2 decreased
by 20% following the addition of 5 mM ouabain to the perfusate. This
ouabain-induced decline in
JtCO2 was
observed both in the presence and in the absence of Sch-28080. We
conclude that total and Sch-28080-sensitive net acid secretion is
increased with dietary K+
restriction. However, since ~50% of
JtCO2 is
insensitive to both Sch-28080 and ouabain, future studies
will be necessary to define other mechanisms of luminal acidification
in the rat tIMCD.
collecting duct; hypokalemia; proton-potassium-adenosinetriphosphatase; HK
1; HK2; ouabain; Sch-28080
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