Developmental regulation of intracellular calcium by N-methyl-D-aspartate and noradrenaline in rat visual cortex

The effects of N-methyl-D-aspartate and noradrenaline on intracellular Ca2 concentration in slices of rat visual cortex were studied using a fluoresc ent indicator, Fura-2. Path application of N-methyl-D-aspartate (1-100 mu M ) increased intracellular Ca2+ concentration in a dose-dependent manner, es pecially in layers II/III. Noradrenaline (1-100 mu M) also increased intrac ellular Ca2+ concentration in a dose-dependent manner, especially in layers I and IV. However, the maximum increase in intracellular Ca2+ concentratio n after 100 mu M noradrenaline application was less than half of that after 100 mu M N-methyl-D-aspartate application in slices obtained from animals in the sensitive period. The effect of noradrenaline was most prominent in slices of the sensitive period, whereas the N-methyl-D-aspartate- induced i ntracellular Ca2+ concentration response decreased with age. Additive effec ts from application of both N-methyl-D-aspartate and noradrenaline on intra cellular Ca2+ concentration were found only in the neonatal stage. Pharmaco logical experiments showed that alpha(1)-adrenergic receptors play a major role in the noradrenaline-induced intracellular Ca2+ concentration response , although both alpha(2)- and beta-adrenegic receptors were also partially involved. The release of Ca2+ from intracellular storage underlay the early phase of the noradrenaline-induced intracellular Ca2+ concentration respon se, while extracellular Ca2+ influxes contributed to the sustained phase. E xperiments using a gliotoxin, fluorocitric acid, suggested that the functio n of glial cells is involved in the noradrenaline-induced increase of intra cellular Ca2+ concentration. The larger intracellular Ca2+ concentration response to noradrenaline durin g the sensitive period may modulate the increase in intracellular Ca2+ conc entration by N-methyl-D-aspartate to maintain a higher level of cortical pl asticity during this period. (C) 1999 IBRO. Published by Elsevier Science L td.