Pharmacological identification of inward current evoked by dopamine in rat subthalamic neurons in vitro.
Neuropharmacology
; 42(6): 772-81, 2002 May.
Article
en En
| MEDLINE
| ID: mdl-12015203
Dopaminergic mechanisms in the subthalamic nucleus (STN) are implicated in the pathophysiology of Parkinson's disease. Here, electrophysiological responses of STN neurons to dopamine (DA) were investigated by using whole-cell patch-clamp recordings in the rat brain slice preparation. Under current-clamp, DA depolarized membrane potential and increased the frequency of spontaneous action potentials of STN neurons. Under voltage-clamp, DA (3-300 microM) produced a reversible concentration-dependent inward current (I(DA); 6-40 pA) with an EC(50) of 13 microM. This DA-induced current had a negative slope conductance which reversed at -102 mV. It was partially reduced by barium and by superfusion with an elevated concentration of extracellular K(+). Moreover, TTX and glutamate receptor antagonists (CNQX and AP5) did not significantly affect the DA responses, indicating that I(DA) is not dependent upon afferent synaptic activity in the STN. Quinpirole, a D(2) receptor agonist, mimicked the DA action more effectively than did the D(1) agonist SKF-38393. The D(2) antagonist sulpiride, but not the D(1) antagonist SCH-23390, blocked responses induced by DA. Intracellular application of G-protein inhibitor GDP-beta-S also suppressed I(DA). GTP-gamma-S, added to the pipette solution, evoked a sustained inward shift in the absence of DA. These results suggest that DA increases the activity of STN neurons via activation of G-protein-coupled D(2)-like receptors which reduce a K(+) conductance.
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Banco de datos:
MEDLINE
Asunto principal:
Potenciales de Acción
/
Dopamina
/
Núcleo Subtalámico
/
Guanosina Difosfato
/
Neuronas
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
Idioma:
En
Revista:
Neuropharmacology
Año:
2002
Tipo del documento:
Article
País de afiliación:
Estados Unidos