ACIDOSIS OF HIPPOCAMPAL-NEURONS MEDIATED BY A PLASMALEMMAL CA2+ H+ PUMP/

MODULATION Of cytosolic calcium ([Ca2+](i)) plays a key role in intrac ellular signalling. In neurones, intracellular Ca2+ transients are inv olved in the regulation of excitability as well as in synaptic transmi ssion and plasticity. Here, we report that depolarization-induced elev ation of [Ca2+](i) evokes a prominent fall of intracellular pH (pH(i)) in voltage-clamped hippocampal pyramidal neurones dialysed with fluor escent indicators of H+ and Ca2+. This acidification is caused by exch ange of internal calcium for extracellular protons via a vanadate- and eosin-sensitive plasmalemmal Ca2+/H+ pump. In view of the potent neur omodulatory actions of H+, these results raise the possibility that ch anges in excitability and synaptic plasticity, hitherto solely attribu ted to Ca2+ transients, may include a significant component mediated b y pH shifts.