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REPORT
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520-8026
Address for reprint requests and other correspondence: W. F. Boron, Dept. of Cellular and Molecular Physiology, Yale Univ. School of Medicine, 333 Cedar St., New Haven, CT 06520 (E-mail: walter.boron{at}yale.edu)
Abstract
The approach that most animal cells employ to regulate intracellular pH (pHi) 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 (ß) of a cell minimizes sudden pHi shifts caused by acute acid and alkali loads. However, increasing C (or ß) only minimizes T (or pHi) changes; it does not eliminate the changes, return T (or pHi) to normal, or shift steady-state T (or pHi). 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 pHi. Whereas an air conditioner lowers T, a cell generally has more than one acid-loading transporter to lower pHi. 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 pHi with graded increases (or decreases) in acid-extrusion (or acid-loading) rate. Steady-state T (or pHi) 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 CO2 or extracellular HCO3 sensors that modulate acid-base transport.
Key words: hydrogen ions; bicarbonate; exchanger; cotransporter
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