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Titolo:
Pharmacological identification of the K+ currents mediating the hypoglycemic hyperpolarization of rat midbrain dopaminergic neurones
Autore:
Marinelli, S; Bernardi, G; Giacomini, P; Mercuri, NB;
Indirizzi:
IRCCS, Clin Santa Lucia, I-00179 Rome, Italy IRCCS Rome Italy I-00179IRCCS, Clin Santa Lucia, I-00179 Rome, Italy Univ Roma Tor Vergata, Neurol Clin, I-00173 Rome, Italy Univ Roma Tor Vergata Rome Italy I-00173 eurol Clin, I-00173 Rome, Italy
Titolo Testata:
NEUROPHARMACOLOGY
fascicolo: 6, volume: 39, anno: 2000,
pagine: 1021 - 1028
SICI:
0028-3908(2000)39:6<1021:PIOTKC>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
VENTROMEDIAL HYPOTHALAMIC NEURONS; SUBSTANTIA-NIGRA NEURONS; POTASSIUM CONDUCTANCE; HIPPOCAMPAL-NEURONS; ZONA COMPACTA; IN-VITRO; ATP; CHANNELS; GLIBENCLAMIDE; TOLBUTAMIDE;
Keywords:
ventral tegmental area; substantia nigra; voltage-clamp; tolbutamide; glibenclamide; charybdotoxin; barium; strophanthidin;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Mercuri, NB IRCCS, Clin Santa Lucia, Via Ardeatina 306, I-00179 Rome, Italy IRCCS Via Ardeatina 306 Rome Italy I-00179 -00179 Rome, Italy
Citazione:
S. Marinelli et al., "Pharmacological identification of the K+ currents mediating the hypoglycemic hyperpolarization of rat midbrain dopaminergic neurones", NEUROPHARM, 39(6), 2000, pp. 1021-1028

Abstract

Hypoglycemia (zero glucose) initially depolarized the membrane and increased the spontaneous firing of rat midbrain dopaminergic neurones (more than 50%) intracellularly recorded in an in vitro slice preparation. Under single-electrode voltage-clamp mode (V-h -55 mV), this transient phase correlated with an inward current of -18 pA. In all the cells tested (n=30), an inhibition fully developed over 16.9 min of hypoglycemia and was associated with a hyperpolarization of the membrane (7.7 mV) or outward current (95.6 pA). Upon re-application of a control solution (glucose 10 mM) a rebound hyperpolarization/outward current developed. The depression of firing was only seen when the artificial cerebrospinal fluid (ACSF) contained less than 1 mMglucose. In addition, the period of time required to block the spontaneousactivity decreased, by diminishing the extracellular concentration of glucose from 1 to 0 mM. The hypoglycemia-induced outward current was associatedwith an increase in membrane conductance and reversed polarity at -100.4 mV, close to the reversal potential of K+. The post-hypoglycemic outward current was not associated with an increase in membrane conductance and did not reverse. The K+-ATP channel blockers, tolbutamide (300 mu M-1 mM) and glibenclamide (3-30 mu M) reduced the hypoglycemia-induced inhibition. In addition, the blocker of the Ca++-activated K+-channels, charybdotoxin (100-400nM) partially counteracted the hypoglycemic hyperpolarization. Furthermore, barium (100-300 mu M) fully antagonized the hypoglycemia-induced inhibition. The post-hypoglycemic hyperpolarization/outward current was not observed in cells treated with the Na+/K+ ATPase pump inhibitor strophanthidin (1-3 mu M) Our data suggest that midbrain dopaminergic cells respond to glucose deprivation with a hyperpolarization generated by the opening of several K+ channels (sulphonylurea-sensitive, charybdotoxin-sensitive and sulphonylurea and charybdotoxin-insensitive) and by the activation of the Na+/K+ ATPase pump after the hypoglycemic period. (C) 2000 Published by Elsevier Science Ltd. All rights reserved.

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Documento generato il 07/07/20 alle ore 17:57:38