Role of bicarbonate in the regulation of intracellular pH in the mammalian ventricular myocyte

Abstract

Bicarbonate is important for pHicontrol in cardiac cells. It is a major part of the intracellular buffer apparatus, it is a substrate for sarcolemmal acid-equivalent transporters that regulate intracellular pH, and it contributes to the pHosensitivity of steady-state pHi, a phenomenon that may form part of a whole-body response to acid/base disturbances. Both bicarbonate and H+/OH–transporters participate in the sarcolemmal regulation of pHi, namely Na+–HCO3–cotransport (NBC), Cl––HCO3–exchange (i.e., anion exchange, AE), Na+–H+exchange (NHE), and Cl––OH–exchange (CHE). These transporters are coupled functionally through changes of pHi, while pHiis linked to [Ca2+]ithrough secondary changes in [Na+]imediated by NBC and NHE. Via such coupling, decreases of pHoand pHican ultimately lead to an elevation of [Ca2+]i, thereby influencing cardiac contractility and electrical rhythm. Bicarbonate is also an essential component of an intracellular carbonic buffer shuttle that diffusively couples cytoplasmic pH to the sarcolemma and minimises the formation of intracellular pH microdomains. The importance of bicarbonate is closely linked to the activity of the enzyme carbonic anhydrase (CA). Without CA activity, intracellular bicarbonate-dependent buffering, membrane bicarbonate transport, and the carbonic shuttle are severely compromised. There is a functional partnership between CA and HCO3–transport. Based on our observations on intracellular acid mobility, we propose that one physiological role for CA is to act as a pH-coupling protein, linking bulk pH to the allosteric H+control sites on sarcolemmal acid/base transporters.Key words: bicarbonate transporter, pHi, heart, ventricular.