title: Effects of potassium channel blockade on endogenous glutamate release from cerebellar slices.
abstract: The effects of potassium channel blockade on the spontaneous release of endogenous glutamate from rat cerebellar slices was studied. Tetrapentylammonium (TPeA), 4-aminopyridine and quinine all increased the spontaneous release of glutamate. The effect of TPeA and 4-AP was potentiated in the absence of Ca2+ from the perfusing fluid. In normal artificial cerebrospinal fluid (ACSF) the Ca2+ channel antagonist, verapamil, mimicked the effects of TPeA seen in Ca2+-free ACSF. The increased release of glutamate produced by TPeA under Ca2+-free conditions was inhibited by the sodium channel blocker, tetrodotoxin, and by Ruthenium red, which inhibits mobilization of mitochondrial Ca2+. The results suggest that external Ca2+ is not required in the TPeA-induced release of glutamate. It is proposed that the prolongation of depolarization seen with potassium channel blocking drugs enables sufficient sodium to enter the neurone and release Ca2+ from intraneuronal stores in order to facilitate transmitter release.
authors.affiliation: Department of Pharmacology and Therapeutics, University of Wales College of Medicine, Cardiff, U.K.
authors.forename: S
authors.initials: S
authors.lastname: Barnes
authors.forename: E M
authors.initials: EM
authors.lastname: Whitham
authors.forename: J A
authors.initials: JA
authors.lastname: Davies
mesh_terms: D015761:4-Aminopyridine; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D066298:In Vitro Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D011803:Quinine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000631:Aminopyridines; D005971:Glutamates; D015221:Potassium Channels; D000644:Quaternary Ammonium Compounds; D018698:Glutamic Acid; C027435:tetrapentylammonium; D011803:Quinine; D015761:4-Aminopyridine