Electrophysiological and morphological analyses of cortical neurons obtained from children with catastrophic epilepsy: dopamine receptor modulation of glutamatergic responses.
The present study examined the electrophysiological effects produced by activation of specific dopamine (DA) receptors and the distribution of DA receptor subtypes and glutamate receptor subunits [N-methyl-D-aspartate (NMDAR1) and GluR1] in cortical tissue samples obtained from children (ages 3 months to 16 years) undergoing epilepsy surgery. DA receptor activation produced differential effects depending on the receptor subtype that was activated. D1 receptor family agonists generally enhanced cortical excitability and favored the emergence of epileptogenic activity. In contrast, D2 receptor family agonists had more variable effects on cortical excitability and the expression of epileptiform discharges. Activation of D1 or D2 receptors decreased the amplitude of non-NMDA-mediated excitatory postsynaptic potentials. In contrast, DA and D1 agonists increased the amplitude of NMDA-mediated potentials. Immunohistochemical analysis showed that the DA receptor subtypes and glutamate receptor subunits examined were present in all cortical layers and areas throughout development. Whole-cell voltage clamp recordings of pyramidal neurons visualized with differential interference contrast optics and infrared videomicroscopy indicated that these neurons displayed a persistent Na(+) current, followed by an outward current. DA reduced the outward current but had little effect on the persistent Na(+) current. These results suggest a dual role for DA's actions in the human cerebral cortex. Activation of D2 receptors or antagonism of D1 receptors may help control seizures in children.
Cepeda
C
C
Mental Retardation Research Center, UCLA, Los Angeles, CA 90024, USA.
Li
Z
Z
Cromwell
H C
HC
Altemus
K L
KL
Crawford
C A
CA
Nansen
E A
EA
Ariano
M A
MA
Sibley
D R
DR
Peacock
W J
WJ
Mathern
G W
GW
Levine
M S
MS
D000293:Adolescent; D002540:Cerebral Cortex / Q000473:pathology* / Q000503:physiopathology*; D002648:Child; D002675:Child, Preschool; D004298:Dopamine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D004594:Electrophysiology; D004827:Epilepsy / Q000473:pathology* / Q000503:physiopathology*; D018698:Glutamic Acid / Q000494:pharmacology / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007223:Infant; D007259:Infrared Rays; D007478:Iontophoresis; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011954:Receptors, Dopamine / Q000502:physiology; D013569:Synapses / Q000502:physiology
D018491:Dopamine Agonists; D011954:Receptors, Dopamine; D018698:Glutamic Acid; D004298:Dopamine