Role of an Electrogenic Na + -HCO 3 − Cotransport in Determining Myocardial pH i After an Increase in Heart Rate

Abstract

The contribution of electrogenic Na + -HCO 3 − 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 CO 2 /HCO 3 − -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 <.05, n=5) in the presence of CO 2 /HCO 3 − 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 CO 2 /HCO 3 − -superfused muscles pretreated with SITS (0.1 mmol/L), this effect of increasing the contraction frequency was reversed, and a decrease of pH i 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 HCO 3 − 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 HCO 3 − -buffered media. This HCO 3 − -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 + -HCO 3 − 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.