TY - JOUR
T1 - A voltage-clamp analysis of NMDA-induced responses on dopaminergic neurons of the rat subtantia nigra zona compacta and ventral tegmental area
AU - Mercuri, Nicola B.
AU - Stratta, Francesca
AU - Calabresi, Paolo
AU - Bernardi, Giorgio
PY - 1992/10/9
Y1 - 1992/10/9
N2 - The effects of NMDA-receptor activation on dopaminergic neurons of the rat substantia nigra zona compacta and ventral tegmental area were studied by using in vitro intracellular electrophysiological recordings (current and voltage-clamp). NMDA depolarized the membrane and increased the firing activity. A voltage-dependent inward current and a reduction of the apparent input conductance were observed in voltage-clamp experiments. Interestingly, the peak amplitude of the inward current occurred at approximately - 60 mV. The NMDA-induced responses were reduced by the application of dl-2-amino-5-phophonovaleric acid (APV). The NMDA-induced current was unaffected by potassium channel blockers, was present in low-sodium solutions or in solutions treated with TTX; but was reduced or blocked in low-calcium solutions containing cobalt. In addition, no reduction of the apparent input conductance was observed either in the solutions without magnesium or in those with low-sodium. Our data indicate that the activation of NMDA receptors produces a powerful excitatory stimulus on the dopaminergic neurons of the ventral mesencephalon and this may be primarily the result of a voltage-dependent influx of calcium ions. The degeneration of the dopaminergic cells after application of neurotoxins may be explained by their peculiar response to NMDA.
AB - The effects of NMDA-receptor activation on dopaminergic neurons of the rat substantia nigra zona compacta and ventral tegmental area were studied by using in vitro intracellular electrophysiological recordings (current and voltage-clamp). NMDA depolarized the membrane and increased the firing activity. A voltage-dependent inward current and a reduction of the apparent input conductance were observed in voltage-clamp experiments. Interestingly, the peak amplitude of the inward current occurred at approximately - 60 mV. The NMDA-induced responses were reduced by the application of dl-2-amino-5-phophonovaleric acid (APV). The NMDA-induced current was unaffected by potassium channel blockers, was present in low-sodium solutions or in solutions treated with TTX; but was reduced or blocked in low-calcium solutions containing cobalt. In addition, no reduction of the apparent input conductance was observed either in the solutions without magnesium or in those with low-sodium. Our data indicate that the activation of NMDA receptors produces a powerful excitatory stimulus on the dopaminergic neurons of the ventral mesencephalon and this may be primarily the result of a voltage-dependent influx of calcium ions. The degeneration of the dopaminergic cells after application of neurotoxins may be explained by their peculiar response to NMDA.
KW - Excitatory amino acid receptor
KW - Intracellular recording
KW - Slice
KW - Ventral mesencephalon
UR - http://www.scopus.com/inward/record.url?scp=0026756814&partnerID=8YFLogxK
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U2 - 10.1016/0006-8993(92)91262-D
DO - 10.1016/0006-8993(92)91262-D
M3 - Article
C2 - 1360865
AN - SCOPUS:0026756814
VL - 593
SP - 51
EP - 56
JO - Brain Research
JF - Brain Research
SN - 0006-8993
IS - 1
ER -