Calcium modulates dopamine potentiation of N-methyl-D-aspartate responses: Electrophysiological and imaging evidence

In the striatum, dopamine (DA) exerts a major modulatory influence on voltage- and ligand-gated currents. Previously we have shown that DA modulates glutamatergic neurotransmission and that the direction of this modulation depends on, among other factors, the glutamate and DA receptor subtypes activated. These effects also involve DA-incluced alterations in voltage-gated Ca2+ currents. In the present experiments, the effects of Ca2+ channel blockers on DA and D1 receptor-dependent potentiation of N-methyl-D-aspartate (NMDA) responses were examined in vitro in striatal slices using current clamp recording techniques. DA or D1 receptor agonists consistently enhanced NMDA responses. Cadmium and the more selective L-type Ca2+ channel antagonists ni-fedipine and methoxyverapamil reduced the potentiation of NMDA responses by DA or D1 receptor activation. Furthermore, studies using Ca2+ imaging with Fluo-3 in cultured cortical or dissociated striatal neurons demonstrated that DA and D1 agonists increased intracellular Ca2+ transients induced by NMDA. These as well as previous findings indicate that in striatal neurons at least two mechanisms contribute to the enhancement of NMDA responses by DA receptor activation, facilitation of voltage-gated Ca2+ currents and D1 receptor activation of the cAMP-protein kinase A cascade. The existence of multiple mechanisms leading to a similar outcome allows a certain degree of redundancy in the consequences of DA modulation. (C) 2004 Wiley-Liss, Inc.