Regulation of intracellular pH

Abstract

The approach that most animal cells employ to regulate intracellular pH (pH(i)) is not too different conceptually from the way a sophisticated system might regulate the temperature of a house. Just as the heat capacity (C) of a house minimizes sudden temperature (T) shifts caused by acute cold and heat loads, the buffering power (beta) of a cell minimizes sudden pH(i) shifts caused by acute acid and alkali loads. However, increasing C (or beta) only minimizes T (or pH(i)) changes; it does not eliminate the changes, return T (or pH(i)) to normal, or shift steady-state T (or pH(i)). Whereas a house may have a furnace to raise T, a cell generally has more than one acid-extruding transporter (which exports acid and/or imports alkali) to raise pH(i). Whereas an air conditioner lowers T, a cell generally has more than one acid-loading transporter to lower pH(i). Just as a house might respond to graded decreases (or increases) in T by producing graded increases in heat (or cold) output, cells respond to graded decreases (or increases) in pH(i) with graded increases (or decreases) in acid-extrusion (or acid-loading) rate. Steady-state T (or pH(i)) can change only in response to a change in chronic cold (or acid) loading or chronic heat (or alkali) loading as produced, for example, by a change in environmental T (or pH) or a change in the kinetics of the furnace (or acid extrudes) or air conditioner (or acid loaders). Finally, just as a temperature-control system might benefit from environmental sensors that provide clues about cold and heat loading, at least some cells seem to have extracellular CO(2) or extracellular HCO(3)(-) sensors that modulate acid-base transport.