Intracellular pH Is Regulated by Buffers and Ion Pumps
Whereas the hemoglobin and bicarbonate provide the most immediately available source of buffers to prevent drastic changes in blood pH, intracellular buffers within the body tissues, other than blood, provide another large reserve of buffering capacity.
In order to enter cells, hydrogen ion must be exchanged with other cations, such as sodium or potassium. Once inside the cell, hydrogen ion is buffered by amino acids, peptides, proteins, and organic phosphates. These buffers provide approximately five times the buffering capacity of the extracellular fluid. As a general rule, intracellular pH follows extracellular pH but because of the large intracellular buffering capacity, the pH changes are less dramatic in the cytosol.Two acid-base ion pumps play a major role in regulation of intracellular pH. The Na'/H' exchanger uses the energy derived from the extracellular to intracellular Na' gradient to move H+ out of the cell and the CΓ∕HCOf exchanger uses a similar mechanism to move HCO3 out of the cell.
When H, concentration within the cell increases, the activity of the Na^-Hl pump increases so that more H4 is extruded. At the same time, the activity of the Cl--HCO3- pump is inhibited so that HCO3 accumulates within the cell. These two mechanisms can restore intracellular pH to normal as long as extracellular pH also is normal. If however, extracellular pH is low, it is more difficult for the Na’-H4 pump to extrude H', and thus intracellular pH lends also to be acidic. If the cytosol becomes alkaline, the activity of the Cl--HCO3- pump is facilitated, and the Na -H pump is inhibited to restore pH. This corrective action is inhibited if extracellular pH also is alkaline.