Calcium Assists Dopamine Release by Preventing Aggregation on the Inner Leaflet of Presynaptic Vesicles.
In this study, the dopamine-lipid bilayer interactions were probed with three physiologically relevant ion compositions using atomistic molecular dynamics simulations and free energy calculations. The in silico results indicate that calcium is able to decrease significantly the binding of dopamine to a neutral (zwitterionic) phosphatidylcholine lipid bilayer model mimicking the inner leaflet of a presynaptic vesicle. We argue that the observed calcium-induced effect is likely in crucial role in the neurotransmitter release from the presynaptic vesicles docked in the active zone of nerve terminals. The inner leaflets of presynaptic vesicles, which are responsible for releasing neurotransmitters into the synaptic cleft, are mainly composed of neutral lipids such as phosphatidylcholine and phosphatidylethanolamine. The neutrality of the lipid head group region, enhanced by a low pH level, should limit membrane aggregation of transmitters. In addition, the simulations suggest that the high calcium levels inside presynaptic vesicles prevent even the most lipophilic transmitters such as dopamine from adhering to the inner leaflet surface, thus rendering unhindered neurotransmitter release feasible.
Department of Physics, Tampere University of Technology , P.O. Box 692, FI-33101 Tampere, Finland.
Sini
S
Mokkila
Structural Bioinformatics Laboratory, Biochemistry, Faculty of Science and Engineering, Åbo Akademi University , 20500 Turku, Finland.
Pekka A
PA
Postila
Department of Physics, Tampere University of Technology , P.O. Box 692, FI-33101 Tampere, Finland.
Sami
S
Rissanen
Department of Physics, Tampere University of Technology , P.O. Box 692, FI-33101 Tampere, Finland.
Hanna
H
Juhola
Department of Physics, Tampere University of Technology , P.O. Box 692, FI-33101 Tampere, Finland.|Department of Physics, University of Helsinki , P.O. Box 64, FI-00014 Helsinki, Finland.|MEMPHYS - Center for Biomembrane Physics, University of Southern Denmark , 5230 Odense, Denmark.
Ilpo
0000-0001-7408-3214
I
Vattulainen
Department of Physics, Tampere University of Technology , P.O. Box 692, FI-33101 Tampere, Finland.|Department of Physics, University of Helsinki , P.O. Box 64, FI-00014 Helsinki, Finland.
Tomasz
0000-0001-6765-7013
T
Róg
D002118:Calcium / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D008051:Lipid Bilayers / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D017729:Presynaptic Terminals / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
D008051:Lipid Bilayers; D002118:Calcium; D004298:Dopamine
Synaptic neurotransmission; binding free energy; dopamine; molecular dynamics simulations; neurotransmitter release; phosphatidylcholine; presynaptic vesicle