Evidence for an electrogenic Na+/HCO3+ cotransporter in cardiac myocytes

E. A. Aiello, H. E. Cingolani

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The Na+/HCO3- cotransporter regulates intracellular pH (pHj) by moving two (n=2) or three (n=3) HCO3- per each Na+ across the membrane. This generates a net flux of negative charge that confers electrogenic characteristics to this transport mechanism. Although the presence of an electrogenic Na+/HCO3- Cotransporter has been identified in most tissues and cell types, in cardiac tissue the electrogenicity of this system is controversial. In this study, we used the nystatin-perforated whole cell configuration of patch clamp technique to determine the activity of the Na+/HCO3" co-transporter in isolated cat ventricular myocytes. Switching from HEPES to HCO3" buffer caused a hyperpolarization of resting membrane potential (Em) by 2.98 ±0.28 (n=5, p0.05) and shortened APD by 43.3 ±7.7% and 30.1 ± 4.6% of the value in HEPES (n=4, p0.05), measured at 50% (AP50) and 90% (APD90) of depolarization, respectively. The hyperpolarization and APD shortening induced by CO2\HCO3 were both reversed by the anionic flux blocker, SITS (0.1 mM), and prevented by replacement of the extracellular Na+ with Li+. Quasi steady-state currents were evoked by 8 s duration voltage-clamped ramps ranging between -130 to +30 mV, from a holding potential of -70 mV. The development of a novel component of steady-state outward current was observed in the presence of HCO3~. Extracellular HCO3~ also induced a 2.89 ±0.57 mV (n=7, p 0.05) negative shin in the reversal potential for net current, consistent with a hyperpolarization of Em. Accordingly, we conclude that Na+/HCO3" co-transporter is electrogenic and has an influence on myocardial resting membrane potential and action potential waveform.

Original languageEnglish (US)
Number of pages1
JournalProceedings of the Western Pharmacology Society
StatePublished - Dec 1 1997

ASJC Scopus subject areas

  • Pharmacology


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