Role of an electrogenic Na(+)-HCO3- cotransport in determining myocardial pHi after an increase in heart rate.

The contribution of electrogenic Na(+)-HCO3- cotransport to pHi 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 pHi from 7.13 +/- 0.03 to 7.36 +/- 0.03 (P < .05, n = 5) in the presence of CO2/ HCO3- buffer. The same increase in the frequency of stimulation, however, decreased pHi 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 pHi 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 mumol/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 bicarbonate influxes, substantially increase the myocardial cell's ability to recover from an enhanced proton production.