title: Evidence from renal proximal tubules that HCO3- and solute reabsorption are acutely regulated not by pH but by basolateral HCO3- and CO2.
abstract: Respiratory acidosis, a decrease in blood pH caused by a rise in [CO(2)], rapidly triggers a compensatory response in which the kidney markedly increases its secretion of H(+) from blood to urine. However, in this and other acid-base disturbances, the equilibrium CO(2) + H(2)O HCO(3)(-) + H(+) makes it impossible to determine whether the critical parameter is [CO(2)], [HCO(3)(-)], and/or pH. Here, we used out-of-equilibrium CO(2)/HCO(3)(-) solutions to alter basolateral (BL) [HCO(3)(-)], [CO(2)], or pH, systematically and one at a time, on isolated perfused S2 rabbit proximal tubules. We found that increasing [HCO(3)(-)](BL) from 0 to 44 mM, at a fixed [CO(2)](BL) of 5% and a fixed pH(BL) of 7.40, caused HCO(3)(-) reabsorption (J(HCO(3))) to fall by half but did not significantly affect volume reabsorption (J(V)). Increasing [CO(2)](BL) from 0% to 20%, at a fixed [HCO(3)(-)](BL) of 22 mM and pH(BL) of 7.40, caused J(HCO(3)) to rise 2.5-fold but did not significantly affect J(V). Finally, increasing pH(BL) from 6.80 to 8.00, at a fixed [HCO(3)(-)](BL) of 22 mM and [CO(2)](BL) of 5%, did not affect either J(HCO(3)) or J(V). Analysis of the J(HCO(3)) and J(V) data implies that, as the tubule alters J(HCO(3)), it compensates the reabsorption of other solutes to keep J(V) approximately constant. Because the cells cannot respond acutely to pH changes, we propose that the responses of J(HCO(3)) and the reabsorption of other solutes to changes in [HCO(3)(-)](BL) or [CO(2)](BL) involve sensors for basolateral HCO(3)(-) and CO(2).
authors.affiliation: Department of Cellular and Molecular Physiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
authors.forename: Yuehan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Jinhua
authors.initials: J
authors.lastname: Zhao
authors.forename: Patrice
authors.initials: P
authors.lastname: Bouyer
authors.forename: Walter F
authors.initials: WF
authors.lastname: Boron
mesh_terms: D000042:Absorption; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D002245:Carbon Dioxide / Q000378:metabolism*; D005260:Female; D006863:Hydrogen-Ion Concentration; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D011817:Rabbits
chemical_list: D001639:Bicarbonates; D002245:Carbon Dioxide
references.citation: Am J Physiol. 1953 Oct;175(1):33-8
references.pmid: 13114345
references.citation: Am J Physiol. 1988 Dec;255(6 Pt 1):C857-69
references.pmid: 3202154
references.citation: Am J Physiol Cell Physiol. 2004 Dec;287(6):C1493-526
references.pmid: 15525685
references.citation: Annu Rev Physiol. 2002;64:899-923
references.pmid: 11826292
references.citation: Am J Physiol Renal Physiol. 2003 Aug;285(2):F359-69
references.pmid: 12734099
references.citation: Crit Care. 2003 Aug;7(4):R60
references.pmid: 12930557
references.citation: Pflugers Arch. 2004 Feb;447(5):495-509
references.pmid: 14722772
references.citation: J Physiol. 2004 Aug 15;559(Pt 1):85-101
references.pmid: 15194736
references.citation: Am J Physiol. 1966 Jun;210(6):1293-8
references.pmid: 5923067
references.citation: Clin Chem. 1976 Feb;22(2):243-5
references.pmid: 1248128
references.citation: Biochem J. 1976 Mar 15;154(3):597-604
references.pmid: 942389
references.citation: Kidney Int. 1977 Jul;12(1):1-8
references.pmid: 894911
references.citation: Biochemistry. 1979 May 29;18(11):2210-8
references.pmid: 36128
references.citation: Am J Physiol. 1980 Jun;238(6):F445-51
references.pmid: 7386625
references.citation: Am J Physiol. 1980 Oct;239(4):F307-F318
references.pmid: 6775539
references.citation: Physiol Rev. 1981 Apr;61(2):296-434
references.pmid: 7012859
references.citation: J Clin Invest. 1982 Sep;70(3):639-49
references.pmid: 6809795
references.citation: Am J Physiol. 1982 Oct;243(4):F335-41
references.pmid: 7124948
references.citation: J Cell Biol. 1982 Oct;95(1):189-96
references.pmid: 6815204
references.citation: Am J Physiol. 1983 Feb;244(2):F165-71
references.pmid: 6401934
references.citation: J Gen Physiol. 1983 Jan;81(1):53-94
references.pmid: 6833997
references.citation: Adv Pediatr. 1983;30:401-71
references.pmid: 6424418
references.citation: J Gen Physiol. 1985 Mar;85(3):443-70
references.pmid: 2985737
references.citation: J Cell Biol. 1986 Mar;102(3):967-71
references.pmid: 3949885
references.citation: Am J Physiol. 1990 Feb;258(2 Pt 2):F429-32
references.pmid: 2106795
references.citation: Am J Physiol. 1990 Mar;258(3 Pt 1):C461-9
references.pmid: 2107748
references.citation: Proc Natl Acad Sci U S A. 1990 Jun;87(12):4742-5
references.pmid: 2162055
references.citation: J Clin Invest. 1991 Aug;88(2):368-74
references.pmid: 1864951
references.citation: J Physiol. 1991 Dec;444:703-21
references.pmid: 1822566
references.citation: Am J Physiol. 1995 Feb;268(2 Pt 2):F179-92
references.pmid: 7864155
references.citation: Am J Physiol. 1995 Feb;268(2 Pt 2):F193-203
references.pmid: 7864156
references.citation: Nature. 1995 Apr 13;374(6523):636-9
references.pmid: 7715702
references.citation: Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6274-8
references.pmid: 7541536
references.citation: Annu Rev Biochem. 1995;64:375-401
references.pmid: 7574487
references.citation: Annu Rev Physiol. 1996;58:427-45
references.pmid: 8815802
references.citation: Nature. 1997 May 22;387(6631):409-13
references.pmid: 9163427
references.citation: Am J Physiol. 1997 Oct;273(4 Pt 2):F595-600
references.pmid: 9362337
references.citation: Proc Natl Acad Sci U S A. 1998 May 26;95(11):6337-42
references.pmid: 9600966
references.citation: Am J Physiol. 1998 May;274(5 Pt 2):F883-8
references.pmid: 9612325
references.citation: Nat Genet. 1998 Jul;19(3):282-5
references.pmid: 9662405
references.citation: Am J Physiol. 1998 Oct;275(4 Pt 2):R1152-63
references.pmid: 9756546
references.citation: J Clin Invest. 1954 Jan;33(1):82-90
references.pmid: 13117969
references.citation: Am J Physiol. 1987 Jul;253(1 Pt 2):F89-94
references.pmid: 3605353
references.citation: Am J Physiol. 1988 Dec;255(6 Pt 1):C844-56
references.pmid: 2849306
references.citation: Nat Genet. 1999 Jan;21(1):84-90
references.pmid: 9916796