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Potassium Channel Activators Decrease Endogenous Glutamate Release from Rat Cerebellar Slices

Overview
Journal Amino Acids
Specialty Biochemistry
Date 2013 Nov 5
PMID 24186325
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Abstract

The effects of the sulphonylurea activators of ATP-sensitive potassium channels (K(+) ATP), cromakalim and pinacidil, on the evoked-release of endogenous glutamate from superfused slices of rat cerebellum was examined. K(+)-stimulated release was Ca(2+)-dependent, whereas tetrapentylammonium (TPeA)-evoked release occurred both in the presence and absence of Ca(2+), but was significantly greater in Ca(2+)-free medium. The Ca(2+)-dependent TPeA and K(+)-evoked release of glutamate was inhibited by both cromakalim and pinacidil in a concentration-dependent fashion. However, although cromakalim markedly reduced Ca(2+)-independent TPeA-evoked release, pinacidil was ineffective. In addition, the vehicle for cromakalim, ethanol, markedly potentiated both Ca(2+)-dependent and -independent TPeA-evoked release, but not K(+)-evoked release. Despite a high concentration of sulphonylurea binding sites and a dense glutamatergic innervation, the concentrations of K(+) ATP channel activators required to inhibit stimulus-evoked release from the cerebellum are higher than those reported to inhibit glutamate release or reduce neuronal activity in other parts of the CNS.

References
1.
Mourre C, Widmann C, Lazdunski M . Sulfonylurea binding sites associated with ATP-regulated K+ channels in the central nervous system: autoradiographic analysis of their distribution and ontogenesis, and of their localization in mutant mice cerebellum. Brain Res. 1990; 519(1-2):29-43. DOI: 10.1016/0006-8993(90)90057-i. View

2.
Schmid-Antomarchi H, De Weille J, Fosset M, Lazdunski M . The receptor for antidiabetic sulfonylureas controls the activity of the ATP-modulated K+ channel in insulin-secreting cells. J Biol Chem. 1987; 262(33):15840-4. View

3.
Gandolfo G, Romettino S, Gottesmann C, van Luijtelaar G, Coenen A, Bidard J . K+ channel openers decrease seizures in genetically epileptic rats. Eur J Pharmacol. 1989; 167(1):181-3. DOI: 10.1016/0014-2999(89)90762-0. View

4.
Ben-Ari Y . Modulation of ATP sensitive K+ channels: a novel strategy to reduce the deleterious effects of anoxia. Adv Exp Med Biol. 1990; 268:481-9. DOI: 10.1007/978-1-4684-5769-8_53. View

5.
Daniell L, Brass E, Harris R . Effect of ethanol on intracellular ionized calcium concentrations in synaptosomes and hepatocytes. Mol Pharmacol. 1987; 32(6):831-7. View