Functional diversity of electrogenic Na+–HCO3− cotransport in ventricular myocytes from rat, rabbit and guinea pig

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Abstract
The Na+–HCO3− 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; 1HCO3− : 1Na+; coupling coefficient N= 1) or electrogenic forms of the transporter (NBCe; equivalent to 2HCO3− : 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 pHi while hyperpolarization decreased it, effects seen only in CO2/HCO3−‐buffered solutions, and blocked by S0859 (cardiac NBC inhibitor). Species differences in amplitude of these pHi changes were rat > guinea pig ≈ rabbit. Tonic depolarization (−140 mV to −0 mV) accelerated NBC‐mediated pHi recovery from an intracellular acid load. At 0 mV, NBC‐mediated outward current at resting pHi 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 pHi‐recovery from an acid load although it was slowed significantly, suggesting electroneutral NBC may also be operational. NBC‐mediated pHi 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.

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