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COUPLED ATP & POTASSIUM EFFLUX FROM INTERCALATED CELLS
Author(s) -
Holtzclaw J. David,
Hatcher Lori I.,
Cornelius Ryan,
Sansom Steven C.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1041.34
Subject(s) - bk channel , efflux , secretion , potassium channel , endocrinology , medicine , purinergic receptor , reabsorption , chemistry , biophysics , adenosine , biology , biochemistry , kidney
We have previously reported that when placed on a high‐K diet, mice lacking the β4 subunit of the large conductance, calcium‐activated potassium channel (BK), BK‐β4 −/− or Kcnmb4 −/− , have decreased K secretion and Na and fluid retention ( J Am Soc Nephrol 2010; 21: 634–645). Since BK‐β4 channels are localized to intercalated cells (IC) in the distal nephron, their role in K secretion and Na reabsorption remains puzzling. However, another report shows that IC are a primary source for lumenal ATP ( J Am Soc Nephrol 2009; 20: 1724–1732). Purinergic signaling plays a role in Na and water retention in the kidney. We hypothesized that in response to high lumenal flow, IC release K and ATP to maintain electrochemical balance. To test this, we placed wild type (WT) and BK‐β4 −/− mice on a normal (0.6% K) or K‐adapted (5% K; KA) diet for 10 days to simulate high tubule flow and measured urine ATP secretion. Analysis revealed that KA WT mice increased ATP secretion 3‐fold (120.6 vs 41.6 fmol/min, P<0.001, N=10) compared to KA BK‐β4 −/− mice. Furthermore, using a cell culture model of IC (C11‐MDCK cells), we shown that 10 dynes/cm 2 induced ATP and K efflux, both of which were inhibited by either 300 μM suramin or BK‐β4 siRNA, but not non‐target siRNA. Likewise, 25 μM Carbenoxolone, a gap junction blocker, also blocked shear‐induced K and ATP efflux. These data suggest coupled electrochemical efflux between K and ATP in IC. Supported by NIH/NIDDK grant R01DK71014 (SCS).