Dramatic effects of external alkalinity on neuronal calcium recovery following a short‐duration glutamate challenge: the role of the plasma membrane Ca²⁺/H⁺ pump

Abstract

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 pHo from 7.4 to 8.5 following a I-min glutamate or NMDA challenge caused a dramatic delay in [Ca2+h recovery which in some cases was accompanied by an additional increase in [Ca2+h. Normalization of pHo, or removal of Ca2+ from the alkaline solution allowed [Ca 2 +h to decrease rapidly again. External alkalinity did not affect the initial rapid decline in [Ca2+)j following a 25 mM K+ pulse. In cerebellar granule cells, the alkaline pHo considerably increased the 4SCa2+ uptake both at rest and following a 2-min GLU pulse. A comparison of these effects of alkaline pHo 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.