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Distinguishing HCO 3 ‐ from CO 3 = transport by the electrogenic Na/HCO 3 cotransporter NBCe1 (SLC4A4) (1098.7)
Author(s) -
Moss Fraser,
Lee Seong,
Parker Mark,
Boron Walter
Publication year - 2014
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.28.1_supplement.1098.7
Subject(s) - chemistry , conductance , cotransporter , analytical chemistry (journal) , extracellular , sodium , physics , chromatography , biochemistry , organic chemistry , condensed matter physics
Theoretically, the electrogenic NBCe1 (SLC4A4), could operate by five thermodynamically equivalent mechanisms: (1) 1 Na + + 2 HCO 3 ‐ , (2) 1 Na + + 1 CO 3 = , (3) NaCO 3 ‐ ion pair uptake, (4) 1 Na + + 1 HCO 3 ‐ uptake with 1 H + extruded, and (5) CO 2 /HCO 3 ‐ ‐stimulated extrusion of 2 H + . We obtained current‐voltage (I‐V) relationships from NBCe1 expressing oocytes superfused with out‐of‐equilibrium (OOE) solutions that vary extracellular pH (pH o ) from 9.0 to 6.0 at a constant [CO 2 ] o and [HCO 3 ‐ ] o . Ignoring direct pH o effects on NBCe1, #1 predicts under constant [CO 2 ] o & [HCO 3 ‐ ] o , E rev will not change. #4 & #5 predict graded decreases in pH o produce steep graded decreases in H + efflux that manifest as steep graded decreases in slope conductance ( G NBC ) and inward rectification. #2 & #3 predict pH o decreases will act by lowering [CO 3 = ] o and [NaCO 3 ‐ ] o , thereby reducing G NBC as predicted by the Michaelis‐Menten equation; the I‐V relationship will remain linear. We find that E rev shifts appropriately for pH o 9.0‐6.0, excluding #1. Importantly, the I‐Vs are linear and exhibit only small G NBC decreases at low pH o , eliminating #4 & #5. In fact ‐‐ based on the experimentally determined K m (CO 3 = ) = 4 μM (constant pH o 7.5 and 5% CO 2 )‐‐ these G NBC decreases at low pH o , and the increases at high pH o are smaller than expected. In conclusion, the major carbon substrate for NBCe1 must be either CO 3 = or NaCO 3 ‐ and, extreme pH o paradoxically modulates NBCe1 to minimize changes in transport rate. Grant Funding Source : Supported by NIH DK30344 and NS18400