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-induced alterations in voltage-gated Ca(2+) currents. In the present experiments, the effects of Ca(2+) 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 Ca(2+) channel antagonists nifedipine and methoxyverapamil reduced the potentiation of NMDA responses by DA or D1 receptor activation. Furthermore, studies using Ca(2+) imaging with Fluo-3 in cultured cortical or dissociated striatal neurons demonstrated that DA and D1 agonists increased intracellular Ca(2+) 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 Ca(2+) 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.
Liu
J C
JC
Mental Retardation Research Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, USA.
DeFazio
R A
RA
Espinosa-Jeffrey
A
A
Cepeda
C
C
de Vellis
J
J
Levine
M S
MS
D000367:Age Factors; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D004298:Dopamine / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology; D016202:N-Methylaspartate / Q000378:metabolism*; D017072:Neostriatum / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
D015220:Calcium Channels; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D004298:Dopamine