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Functional diversity of electrogenic Na + –HCO 3 − cotransport in ventricular myocytes from rat, rabbit and guinea pig
Author(s) -
Yamamoto Taku,
Swietach Pawel,
Rossini Alessandra,
Loh ShihHurng,
VaughanJones Richard D.,
Spitzer Kenneth W.
Publication year - 2005
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2004.071068
Subject(s) - depolarization , hyperpolarization (physics) , guinea pig , biophysics , cotransporter , voltage clamp , membrane potential , chemistry , myocyte , reversal potential , patch clamp , intracellular , intracellular ph , electrophysiology , medicine , biochemistry , endocrinology , biology , sodium , stereochemistry , nuclear magnetic resonance spectroscopy , organic chemistry
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 ≈ 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 ∼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.