Role of alpha-synuclein in presynaptic dopamine recruitment.
Real-time monitoring of stimulated dopamine release in mice with different alpha-synuclein expression was used to study the role of alpha-synuclein in presynaptic dopamine recruitment. Repeated electrical stimulations of ascending dopaminergic pathways decreased the capacity of the readily releasable pool (RRP) and temporarily increased its refilling rate, significantly slowing the rate of dopamine decline in mice with normally expressed alpha-synuclein. Mice with alpha-synuclein null mutation demonstrated a permanent increase of the refilling rate. This increase maintained stable dopamine release during stimulation (which induced dopamine decline in other animals) and served as an adaptation to altered dopamine compartmentalization. Mice without alpha-synuclein and with overexpression of human A30P mutated alpha-synuclein had a lower capacity of the dopamine storage pool than other animals. Reducing capacity of the storage pool in transgenic A30P mice led to paradoxical effects of l-dopa, which elevated dopamine release in response to single stimulation but decreased the refilling rate of the RRP.
Yavich
Leonid
L
Department of Pharmacology and Toxicology, Clinical Research Centre/Mediteknia, University of Kuopio, Finland. leonid.yavich@uku.fi
Tanila
Heikki
H
Vepsäläinen
Saila
S
Jäkälä
Pekka
P
D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D004558:Electric Stimulation; D006801:Humans; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D051843:Synucleins; D013997:Time Factors; D019805:alpha-Methyltyrosine / Q000494:pharmacology; D051844:alpha-Synuclein
D015259:Dopamine Agents; D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; C497605:Snca protein, mouse; D051843:Synucleins; D051844:alpha-Synuclein; D007980:Levodopa; D019805:alpha-Methyltyrosine; D004298:Dopamine