Choline's phosphorylation in rat striatal slices is regulated by the activity of cholinergic neurons.
The mechanism by which populations of brain cells regulate the flux of choline (Ch) into membrane or neurotransmitter biosynthesis was investigated using electrically stimulated superfused slices of rat corpus striatum. [Me-14C]Ch placed in the superfusion medium for 30 min during a 1-h stimulation period was incorporated into tissue [14C] phosphorylcholine (PCh) and [14C]phosphatidylcholine (PtdCh). Stimulation also caused a profound inhibition of PCh synthesis and a 10-fold increase in [14C]ACh release into the medium; it failed to affect tissue [14C]ACh levels. This effect was not explained by changes in ATP levels nor in the kinetic properties of Ch kinase (E.C. 2.7.1.32) or Ch acetyltransferase (ChAT) (E.C.2.3.1.7). To investigate the mechanism of these effects, Ch uptake studies were performed with and without hemicholinium-3 (HC3), a selective inhibitor of high affinity Ch uptake. A two-compartment model accurately fit the observed data and yielded a K(m) for Ch uptake of 5 microM into cholinergic structures and 72 microM into all other cells. Using this model it was estimated that cholinergic neurons account for 60% of observed uptake of Ch at physiologic Ch concentrations, even though they represent fewer than 1% of the total cells in the slice. The model also predicts that an increase in Ch uptake within cholinergic neurons, reported to be associated with depolarization [4,27,32], would significantly inhibit Ch uptake into all other cells, and would account for the observed decrease in PCh synthesis.
Farber
S A
SA
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge 02139, USA.
Savci
V
V
Wei
A
A
Slack
B E
BE
Wurtman
R J
RJ
D000818:Animals; D002794:Choline / Q000378:metabolism*; D002799:Cholinergic Fibers / Q000502:physiology*; D003342:Corpus Striatum / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D008297:Male; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley
D002794:Choline