A homeostatic mechanism counteracting K(+) -evoked choline release in adult brain.
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.
Klein
Jochen
J
Department of Pharmacology, University of Mainz, Mainz, Germany. jklein@mail.uni-mainz.de
Weichel
Oksana
O
Ruhr
Judith
J
Dvorak
Claudia
C
Löffelholz
Konrad
K
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
D026902:Potassium Channel Blockers; D006426:Hemicholinium 3; D015761:4-Aminopyridine; D002794:Choline; D011188:Potassium