DRAMATIC EFFECTS OF EXTERNAL ALKALINITY ON NEURONAL CALCIUM RECOVERY FOLLOWING A SHORT-DURATION GLUTAMATE CHALLENGE - THE ROLE OF THE PLASMA-MEMBRANE CA2+/H+ PUMP

Alkalinization of the external medium has been shown to suppress Ca2+ extrusion from neurons due to inhibition of the plasmalemmal Ca2+/H+ pump, In our experiments on fura-2-loaded rat cerebellar granule cells and mouse hippocampal neurons, an increase in pH(o) from 7.4 to 8.5 following a 1-min glutamate or NMDA challenge caused a dramatic delay in [Ca2+](i) recovery which in some cases was accompanied by an additional increase in [Ca2+](i), Normalization of pH(o), or removal of Ca2+ from the alkaline solution allowed [Ca2+](i) to decrease rapidly again, External alkalinity did not affect the initial rapid decline in [Ca2+](i) following a 25 mM K+ pulse, In cerebellar granule cells, the alkaline pH(o) considerably increased the Ca-45(2+) uptake both at rest and following a 2-min GLU pulse, A comparison of these effects of alkaline pH(o) with those produced by removal of the external Na+ led us to conclude that the Ca2+/H+ pump plays a dominant role in the mechanism of the fast Ca2+ extrusion from glutamate- or NMDA-treated neurons.