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 pHo 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 pHo, 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 mMK+ pulse. In cerebellar granule cells, the alkaline pHo considerably increased the 45Ca2+ 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.
Khodorov
B
B
Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow.
Pinelis
V
V
Vergun
O
O
Storozhevykh
T
T
Fajuk
D
D
Vinskaya
N
N
Arsenjeva
E
E
Khaspekov
L
L
Lyzin
A
A
Isaev
N
N
D000818:Animals; D001921:Brain / Q000166:cytology; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D018698:Glutamic Acid / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008810:Mice, Inbred C57BL; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism
D018698:Glutamic Acid; D016202:N-Methylaspartate; D012964:Sodium; D000252:Calcium-Transporting ATPases; D002118:Calcium