Synergistic interactions between noradrenaline and glutamate in cytosolic calcium influx in cultured visual cortical neurons

Abstract

In primary neuronal cultures derived from the visual cortex of embryonic day 16–18 rats, intracellular free calcium concentration, [Ca 2+] i, was increased by bath application of glutamate in a dose-dependent manner. Noradrenaline applied alone had relatively small effects. However, when glutamate concentrations eliciting modest increases in [Ca 2+] i were applied together with 1 μM noradrenaline, the increase in [Ca 2+] i could be enhanced by a factor of up to eight. The synergistic effect was seen in 147 neurons out of a total of 215 cells observed in 54 experiments. The observed enhancement was much more obvious at low doses of glutamate than with higher doses, augmenting all submaximal calcium responses to similar asymptotic levels. 2-Amino-5-phosphonovalerate (APV), the NMDA receptor antagonist, completely blocked the adrenergic enhancing effect ( 29/29 cells in 8 experiments). Among the antagonists specific to α 1 , α 2 and β subtypes of adrenoceptors, the β antagonist propranolol most completely blocked the enhancing effect ( 13/14 cells in 4 experiments, reducing the effect by an amplitude of 90%). The involvement of the β receptor pathway was further supported by the ability of a cAMP analog to mimic the enhancing effect of noradrenaline. On the other hand, an α 1 blocker showed no effect and an α 2 blocker showed only a relatively small effect. These results suggest that receptors for noradrenaline and glutamate colocalize on postsynaptic cortical cells and that adrenergic modulation of glutamate induced calcium influx most likely operate through the β receptor pathway. It is further postulated that cortical ocular dominance plasticity may be at least partially implemented via a calcium dependent cascade.