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1 Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
2 Division of Pediatric Nephrology, Department of Pediatrics, Mount Sinai School of Medicine, New York, NY, USA
* To whom correspondence should be addressed. E-mail: kleyman{at}pitt.edu.
The CCD is a final site for regulation of K+ homeostasis. CCD K+ secretion is determined
by the electrochemical gradient and apical permeability to K+. Conducting secretory K+
(SK/ROMK) and maxi-K channels are present in the apical membrane of the CCD, the
former in principal cells and the latter in both principal and intercalated cells. Whereas
SK channels mediate baseline K+ secretion, maxi-K channels appear to participate in
flow-stimulated K+ secretion. Chronic dietary K+ loading enhances the CCD K+ secretory
capacity due, in part, to an increase in SK channel density (Palmer et al, J Gen Physiol
104:693, 1994). Long-term exposure of Ambystoma tigrinum to elevated K+ increases
renal K+ excretion due to an increase in apical maxi-K channel density in their CDs
(Stoner and Viggiano, J Membr Biol 162:107, 1998). The purpose of the present study
was to test whether K+ adaptation in the mammalian CCD is associated with upregulation
of maxi-K channel expression. NZW rabbits were fed a low (LK), control (CK), or high
(HK) K+ diet for 10-14 d. Real-time PCR quantitation of message encoding maxi-K
and
2-4 in single CCDs from HK animals was greater than that detected in CK and LK
animals (p < 0.05);
1 subunit was not detected in any CCD sample, but was present in
whole kidney. Indirect immunofluorescence microscopy revealed a predominantly
intracellular distribution of
subunits in LK kidneys. In contrast, robust apical labeling
was detected primarily in
-intercalated cells in HK kidneys. In summary, K+ adaptation
is associated with an increase in steady state abundance of maxi-K channel subunit-specific
mRNAs and immunodetectable apical
subunit, the latter observation consistent
with redistribution from an intracellular pool to the plasma membrane.
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