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Calcium Assists Dopamine Release by Preventing Aggregation on the Inner Leaflet of Presynaptic Vesicles
Tekijät: Mokkila S, Postila PA, Rissanen S, Juhola H, Vattulainen I, Rog T
Kustantaja: AMER CHEMICAL SOC
Julkaisuvuosi: 2017
Journal: ACS Chemical Neuroscience
Tietokannassa oleva lehden nimi: ACS CHEMICAL NEUROSCIENCE
Lehden akronyymi: ACS CHEM NEUROSCI
Vuosikerta: 8
Aloitussivu: 1242
Lopetussivu: 1250
Sivujen määrä: 9
ISSN: 1948-7193
DOI: https://doi.org/10.1021/acschemneuro.6b00395
Tiivistelmä
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 neuro-transmitters 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.
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 neuro-transmitters 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.
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