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Department of Physiology and Biophysics, University of Colorado Health Sciences Center, Aurora, Colorado
Submitted 29 October 2004 ; accepted in final form 31 August 2005
The renal electrogenic Na+-HCO3– cotransporter (hkNBCe1) plays a major role in the bicarbonate reabsorption by the kidney. We examined how PMA- and ANG II-activated PKCs regulate hkNBCe1 expressed with or without the ANG II receptors AT1B in Xenopus laevis oocytes. We found that 10 nM PMA halved the hkNBCe1 current detected in voltage-clamped oocytes. A PKC-specific inhibitor GF-109203X, and a specific inhibitor of Ca-dependent conventional PKC
, GÖ-6976, significantly reduced PMA inhibition. PMA did not alter surface expression of the cotransporters, but it significantly increased hkNBCe1-PKC membrane association. We found that at 10–6 M, ANG II halved the hkNBCe1 current detected in oocytes coexpressing cotransporters with AT1B. A PKC-specific inhibitor GF-109203X, and a PKC
translocation inhibitor V1–2 peptide as well as BAPTA-AM (but not GÖ-6976), significantly reduced ANG II inhibition. At 10–6 M, ANG II significantly decreased surface expression of the cotransporters and increased hkNBCe1-PKC membrane association. Additionally, we found that at 10–11 and 10–10 M ANG II stimulated hkNBCe1 current. This effect was blocked by BAPTA-AM and partially reduced by GF-109203X. We also found that ANG II increased intracellular Ca2+ in fluo 4-loaded oocytes. Our results suggest that 1) PMA inhibition of hkNBCe1 is mediated by Ca-dependent PKC and 10 nM PMA does not induce downregulation of cotransporter surface expression. 2) ANG II (10–6 M) inhibition of hkNBCe1 is mediated by both Ca-independent PKC and downregulation of cotransporter surface expression, possibly triggered by intracellular Ca2+ mobilization. 3) Similar to proximal tubule, acute ANG II has a biphasic effect on hkNBCe1 coexpressed with AT1B in X. laevis oocytes.
PKC; MAPK; intracellular calcium; fluo 4; endocytosis
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