TEMPORAL AND SPATIAL DIFFERENCES IN INTRACELLULAR CA++ CHANGES ELICITED BY K+ AND GLUTAMATE IN SINGLE CULTURED NEOCORTICAL NEURONS

Changes as a function of time in the intracellular Ca++ concentration ([Ca++](i)) in cultured cerebral cortical neurons were monitored after exposure of the cells to either 55 mM KCl or 100 mu M glutamate using the fluorescent Ca++ chelator fura-2. The changes in [Ca++](i) were f ollowed in both cell bodies and neurites. Depolarization with K+ led t o an immediate increase in [Ca++](i) in neurites followed by a slower rise in the cell bodies. In contrast, glutamate elicited a slow increa se in [Ca++](i) in both neurites and cell bodies, and this increase sh owed a plateau rather than a peak as that seen after exposure to K+. T he Ca++ channel blockers verapamil and nifedipine affecting N- and L-t ype channels, respectively had differential effects on K+ stimulated i ncreases in [Ca++](i). Nifedipine only affected the increase marginall y whereas verapamil inhibited the response by 50-60% both in cell bodi es and neurites. The glutamate-induced increase in [Ca++](i) was inhib ited by nifedipine by 60% in neurites whereas no effect was observed i n cell bodies. The results show that depolarization elicited by K+ and glutamate has different effects in different parts of the neurons and that the pharmacological characteristics of voltage gated Ca++ channe ls are dramatically different in cell bodies and neurites. Moreover, t he distribution of L-type channels activated by glutamate differs in c ell bodies and neurites. Such differences in the spatial distribution of Ca++ channels are likely to be of major importance for the function al consequences of depolarization coupled increases in [Ca++](i) such as transmitter release and neurotoxicity. Copyright (C) 1996 Elsevier Science Ltd.