title: A homeostatic mechanism counteracting K(+) -evoked choline release in adult brain.
abstract: Choline (Ch) is an essential nutrient as the biosynthetic precursor of acetylcholine (ACh) and phospholipids. Under resting conditions, the intracellular accumulation of Ch (above 10-fold), which is positively charged, is governed by the membrane potential and follows the Nernst equation. Accordingly, in synaptosomes from adult rats during depolarization, we observed a linear relationship between release of free cytoplasmic Ch and KCl concentration (2.7-120 mm). The K(+) -evoked Ch release was Ca(2+) -independent and did not originate from ACh or phospholipid hydrolysis. In superfused brain slices of adult rats, however, a K(+) -induced Ch efflux was absent. Also, under in vivo conditions, 30-60 mm KCl failed to increase the extracellular Ch level as shown by microdialysis in adult rat hippocampus. On the contrary, in brain slices from 1-week-old rats, high K(+) as well as 4-aminopyridine evoked a marked Ch efflux in a concentration-dependent fashion. This phenomenon faded within 1 week. Hemicholinium-3 (HC-3, 1 and 10 microm), a blocker of cellular choline uptake, caused a marked efflux of choline from adult rat slices but no or significantly less release from immature slices. We conclude that depolarization of synaptic endings causes a Ca(2+) -independent release of free cytoplasmic Ch into the extracellular space. In adult rat brain, this elevation of Ch is counteracted by a homeostatic mechanism such as uptake into brain cells.
authors.affiliation: Department of Pharmacology, University of Mainz, Mainz, Germany. jklein@mail.uni-mainz.de
authors.forename: Jochen
authors.initials: J
authors.lastname: Klein
authors.forename: Oksana
authors.initials: O
authors.lastname: Weichel
authors.forename: Judith
authors.initials: J
authors.lastname: Ruhr
authors.forename: Claudia
authors.initials: C
authors.lastname: Dvorak
authors.forename: Konrad
authors.initials: K
authors.lastname: Löffelholz
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects; D002794:Choline / Q000032:analysis / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000737:chemistry / Q000378:metabolism; D006426:Hemicholinium 3 / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D017551:Microdialysis; D011188:Potassium / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism
chemical_list: D026902:Potassium Channel Blockers; D006426:Hemicholinium 3; D015761:4-Aminopyridine; D002794:Choline; D011188:Potassium