title: Functional diversity of electrogenic Na+-HCO3- cotransport in ventricular myocytes from rat, rabbit and guinea pig.
abstract: The Na(+)-HCO(3)(-) cotransporter (NBC) is an important sarcolemmal acid extruder in cardiac muscle. The characteristics of NBC expressed functionally in heart are controversial, with reports suggesting electroneutral (NBCn; 1HCO(3)(-) : 1Na(+); coupling coefficient N= 1) or electrogenic forms of the transporter (NBCe; equivalent to 2HCO(3)(-) : 1Na(+); N= 2). We have used voltage-clamp and epifluorescence techniques to compare NBC activity in isolated ventricular myocytes from rabbit, rat and guinea pig. Depolarization (by voltage clamp or hyperkalaemia) reversibly increased steady-state pH(i) while hyperpolarization decreased it, effects seen only in CO(2)/HCO(3)(-)-buffered solutions, and blocked by S0859 (cardiac NBC inhibitor). Species differences in amplitude of these pH(i) changes were rat > guinea pig approximately rabbit. Tonic depolarization (-140 mV to -0 mV) accelerated NBC-mediated pH(i) recovery from an intracellular acid load. At 0 mV, NBC-mediated outward current at resting pH(i) was +0.52 +/- 0.05 pA pF(-1) (rat, n= 5), +0.26 +/- 0.05 pA pF(-1) (guinea pig, n= 5) and +0.10 +/- 0.03 pA pF(-1) (rabbit, n= 9), with reversal potentials near -100 mV, consistent with N= 2. The above results indicate a functionally active voltage-sensitive NBCe in these species. Voltage-clamp hyperpolarization negative to the reversal potential for NBCe failed, however, to terminate or reverse NBC-mediated pH(i)-recovery from an acid load although it was slowed significantly, suggesting electroneutral NBC may also be operational. NBC-mediated pH(i) recovery was associated with a rise of [Na(+)](i) at a rate approximately 25% of that mediated via NHE, and consistent with an apparent NBC stoichiometry between N= 1 and N= 2. In conclusion, NBCe in the ventricular myocyte displays considerable functional variation among the three species tested (greatest in rat, least in rabbit) and may coexist with some NBCn activity.
authors.affiliation: Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT 84112, USA. spitzer@cvrti.utah.edu
authors.forename: Taku
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Pawel
authors.initials: P
authors.lastname: Swietach
authors.forename: Alessandra
authors.initials: A
authors.lastname: Rossini
authors.forename: Shih-Hurng
authors.initials: SH
authors.lastname: Loh
authors.forename: Richard D
authors.initials: RD
authors.lastname: Vaughan-Jones
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Spitzer
mesh_terms: D000138:Acidosis / Q000378:metabolism; D000818:Animals; D002021:Buffers; D002138:Calibration; D002469:Cell Separation; D015194:Diffusion Chambers, Culture; D004594:Electrophysiology; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000502:physiology; D032383:Myocytes, Cardiac / Q000378:metabolism*; D009994:Osmolar Concentration; D018408:Patch-Clamp Techniques; D011817:Rabbits; D051381:Rats; D027982:Sodium-Bicarbonate Symporters / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D012996:Solutions; D013045:Species Specificity
chemical_list: D002021:Buffers; D027982:Sodium-Bicarbonate Symporters; D017923:Sodium-Hydrogen Exchangers; D012996:Solutions