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Titolo:
DOPAMINE-INHIBITION - ENHANCEMENT OF GABA ACTIVITY AND POTASSIUM CHANNEL ACTIVATION IN HYPOTHALAMIC AND ARCUATE NUCLEUS NEURONS
Autore:
BELOUSOV AB; VANDENPOL AN;
Indirizzi:
YALE UNIV,SCH MED,NEUROSURG SECT,DEPT NEUROSURG,333 CEDAR ST NEW HAVEN CT 06520 YALE UNIV,SCH MED,NEUROSURG SECT,DEPT NEUROSURG NEW HAVEN CT 06520 STANFORD UNIV,DEPT BIOL SCI STANFORD CA 94305
Titolo Testata:
Journal of neurophysiology
fascicolo: 2, volume: 78, anno: 1997,
pagine: 674 - 688
SICI:
0022-3077(1997)78:2<674:D-EOGA>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
PREFRONTAL CORTICAL-NEURONS; RECEPTOR MESSENGER-RNA; RAT LACTOTROPH CELLS; SYNAPTIC TRANSMISSION; CALCIUM CURRENTS; PYRAMIDAL CELLS; D2 RECEPTORS; GLUTAMATE; INVITRO; CORTEX;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
50
Recensione:
Indirizzi per estratti:
Citazione:
A.B. Belousov e A.N. Vandenpol, "DOPAMINE-INHIBITION - ENHANCEMENT OF GABA ACTIVITY AND POTASSIUM CHANNEL ACTIVATION IN HYPOTHALAMIC AND ARCUATE NUCLEUS NEURONS", Journal of neurophysiology, 78(2), 1997, pp. 674-688

Abstract

Dopamine (DA) decreases activity in many hypothalamic neurons. To determine the mechanisms of DA's inhibitory effect, whole cell voltage-and current-clamp recordings were made from primary cultures of rat hypothalamic and arcuate nucleus neurons (n = 186; 15-39 days in vitro). In normal buffer, DA (usually 10 mu M; n = 23) decreased activity in 56% of current-clamped cells and enhanced activity in 22% of the neurons. In neurons tested in the presence of glutamate receptor antagonists D,L-2-amino-5-phosphonovalerate (AP5; 100 mu M) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 mu M), DA application (10 mu M) revealed heterogeneous effects on electrical activity of cells, either hyperpolarization and decrease in activity (53% of 125) or depolarization and increase in spontaneous activity (22% of 125). The DA-mediated hyperpolarization of membrane potential was associated with a decrease in theinput resistance. The reversal potential for the DA-mediated hyperpolarization was -97 mV, and it shifted in a positive direction when the concentration of K+ in the incubating medium was increased, suggestingDA activation of K+ channels. Because DA did not have a significant effect on the amplitude of voltage-dependent K+ currents, activation ofvoltage-independent K+ currents may account for most of the hyperpolarizing actions of DA. DA-mediated hyperpolarization and depolarizationof neurons were found during application of the Na+ channel blocker tetrodotoxin (1 mu M). The hyperpolarization was blocked by the application of DA D-2 receptor antagonist eticlopride (1-20 mu M; n = 7). In the presence of AP5 and CNQX, DA (10 mu M) increased (by 250%) the frequency of spontaneous inhibitory postsynaptic currents (IPSCs) in 11 of 19 neurons and evoked IPSCs in 7 of 9 cells that had not previously shown any IPSCs. DA also increased the regularity and the amplitude (by 240%) of spontaneous IPSCs in 9 and 4 of 19 cells, respectively. Spontaneous and DA-evoked IPSCs and inhibitory postsynaptic potentials were blocked by the gamma-aminobutyrate A (GABA(A)) antagonist bicuculline (50 mu M), verifying their GABAergic origin. Pertussis toxin pretreatment (200 ng/ml; n = 15) blocked the DA-mediated hyperpolarizations,but did not prevent depolarizations (n = 3 of 15) or increases in IPSCs (n = 6 of 10) elicited by DA. Intracellular neurobiotin injections (n = 21) revealed no morphological differences between cells that showed depolarizing or hyperpolarizing responses to DA. Immunolabeling neurobiotin-filled neurons that responded to DA (n = 13) showed that GABAimmunoreactive neurons (n = 4) showed depolarizing responses to DA, whereas nonimmunoreactive neurons (n = 9) showed both hyperpolarizing (n = 6) and depolarizing (n = 3)responses. DA-mediated hyperpolarization, depolarization, and increases in frequency of postsynaptic activitycould be detected in embryonic hypothalamic or arcuate nucleus neurons after only 5 days in vitro, suggesting that DA could play a modulatory role in early development. These findings suggest that DA inhibition in hypothalamic and arcuate nucleus neurons is achieved in part through the direct inhibition of excitatory neurons, probably via DA D-2 receptors acting through a G(i)/G(o) protein on K+ channels, and in part through the enhancement of GPLBAergic neurotransmission.

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Documento generato il 19/01/20 alle ore 06:10:20