These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Pharmacological identification of the K(+) currents mediating the hypoglycemic hyperpolarization of rat midbrain dopaminergic neurones.
    Author: Marinelli S, Bernardi G, Giacomini P, Mercuri NB.
    Journal: Neuropharmacology; 2000 Apr 03; 39(6):1021-8. PubMed ID: 10727712.
    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 mM glucose. In addition, the period of time required to block the spontaneous activity decreased, by diminishing the extracellular concentration of glucose from 1 to 0 mM. The hypoglycemia-induced outward current was associated with 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 microM-1 mM) and glibenclamide (3-30 microM) reduced the hypoglycemia-induced inhibition. In addition, the blocker of the Ca(++)-activated K(+)-channels, charybdotoxin (100-400 nM) partially counteracted the hypoglycemic hyperpolarization. Furthermore, barium (100-300 microM) 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 microM). 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.
    [Abstract] [Full Text] [Related] [New Search]