Role of an electrogenic Na⁺-HCO₃^- cotransport in determining myocardial pH(i) after an increase in heart rate

The contribution of electrogenic Na⁺-HCO₃^- cotransport to pH(i) regulation during changes in heart rate was explored in cat papillary muscles loaded with BCECF-AM in bicarbonate free (HEPES) medium and in CO₂/HCO₃^- buffered medium. Stepwise increments in the frequency of contraction from 15 to 100 bpm induced a reversible increase in the pH(i) from 7.13±0.03 to 7.36±0.03 (P<0.5, n=5) in the presence of CO₂/HCO₃^- buffer. The same increase in the frequency of stimulation, however, decreased pH(i) from 7.10±0.02 to 6.91±0.06 (P<.05, n=5), in the absence of bicarbonate. Moreover, in CO₂/HCO₃^--superfused muscles pretreated with SITS (0.1 mmol/L), this effect of increasing the contraction frequency was reversed, and a decrease of pH₁, from 7.03±0.04 to 6.88±0.06 (P<.05, n=4) was observed when the pacing rate was increased stepwise from 15 to 100 bpm. High [K⁺](o)-induced depolarization of cell membrane alkalinized myocardial cells in the presence of HCO₃^- ions, whereas acidification was observed as a consequence of hyperpolarization induced by low external [K⁺](o). Myocardial resting membrane potential became hyperpolarized upon exposure to HCO₃^-- buffered media. This HCO₃^--induced hyperpolarization was not blocked by the inhibition of Na⁺,K⁺-ATPase activity by ouabain (0.5 μmol/L) but was prevented by SITS. The results suggested that membrane depolarization during cardiac action potential causes an increase in electrogenic Na⁺-HCO₃^- cotransport. Such depolarizations occurring as a consequence of increases in heart rate would thus, by means of elevated bicarbomate influxes, substantially increase the myocardial cell's ability to recover from an enhanced proton production.