We investigated the cytosolic free calcium concentration ([Ca2+](i)) of lee
ch Retzius neurons in situ while varying the extracellular Ca2+ concentrati
on via the bathing solution ([Ca2+](B))- Changing [Ca2+](B) had only an eff
ect on [Ca2+](i) if the cells were depolarized by raising the extracellular
K+ concentration. Surprisingly raising [Ca2+](B) from 2 to 10 mm caused a
decrease in [Ca2+](i), and an increase was evoked by reducing [Ca2+](B) to
0.1 mM. These changes were not due to shifts in membrane potential. At low
[Ca2+](B) moderate membrane depolarizations were sufficient to evoke a [Ca2
+](i) increase, while progressively larger depolarizations were necessary a
t higher [Ca2+](B). The changes in the relationship between [Ca2+](i) and m
embrane potential upon varying [Ca2+](B) could be reversed by changing extr
acellular pH. We conclude that [Ca2+](B) affects [Ca2+](i) by modulating Ca
2+ influx through voltage-dependent Ca2+ channels via the electrochemical C
a2+ gradient and the surface potential at the extracellular side of the pla
sma membrane. These two parameters are affected in a counteracting way: Rai
sing the extracellular Ca2+ concentration enhances the electrochemical Ca2 gradient and hence Ca2+ influx, but it attenuates Ca2+ channel activity by
shifting the extracellular surface potential to the positive direction, an
d vice versa.