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(Circulation Research. 1996;79:698-704.)
© 1996 American Heart Association, Inc.

Articles

Role of an Electrogenic Na⁺-HCO₃^- Cotransport in Determining Myocardial pH_i After an Increase in Heart Rate

Maria C. Camilion de Hurtado, Bernardo V. Alvarez, Nestor G. Perez, Horacio E. Cingolani

Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Medicas, Universidad Nacional de La Plata (Argentina).

Correspondence to Dr Horacio E. Cingolani, Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Medicas, Universidad Nacional de La Plata, Calle 60 y 120, 1900 La Plata, Argentina.

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<.05, 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 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 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 bicarbonate influxes, substantially increase the myocardial cell's ability to recover from an enhanced proton production.

Key Words: Na⁺-HCO₃^- cotransport • BCECF • pH_i • membrane potential • heart rate

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