A voltage-clamp analysis of NMDA-induced responses on dopaminergic neurons of the rat substantia nigra zona compacta and ventral tegmental area.
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-phosphonovaleric 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.
Clinica Neurologica, II Università di Roma, Italy.
N B
NB
Mercuri
F
F
Stratta
P
P
Calabresi
G
G
Bernardi
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D004553:Electric Conductivity / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000494:pharmacology; D013378:Substantia Nigra / Q000502:physiology*; D013681:Tegmentum Mesencephali / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D013779:Tetrodotoxin; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D012964:Sodium; D002118:Calcium; D004298:Dopamine