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Calcium Assists Dopamine Release by Preventing Aggregation on the Inner Leaflet of Presynaptic Vesicles

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Calcium Assists Dopamine Release by Preventing Aggregation on the Inner Leaflet of Presynaptic Vesicles. / Mokkila, Sini; Postila, Pekka A.; Rissanen, Sami; Juhola, Hanna; Vattulainen, Ilpo; Róg, Tomasz.

In: ACS Chemical Neuroscience, Vol. 8, No. 6, 21.06.2017, p. 1242-1250.

Research output: Contribution to journalArticleScientificpeer-review

Harvard

Mokkila, S, Postila, PA, Rissanen, S, Juhola, H, Vattulainen, I & Róg, T 2017, 'Calcium Assists Dopamine Release by Preventing Aggregation on the Inner Leaflet of Presynaptic Vesicles', ACS Chemical Neuroscience, vol. 8, no. 6, pp. 1242-1250. https://doi.org/10.1021/acschemneuro.6b00395

APA

Mokkila, S., Postila, P. A., Rissanen, S., Juhola, H., Vattulainen, I., & Róg, T. (2017). Calcium Assists Dopamine Release by Preventing Aggregation on the Inner Leaflet of Presynaptic Vesicles. ACS Chemical Neuroscience, 8(6), 1242-1250. https://doi.org/10.1021/acschemneuro.6b00395

Vancouver

Mokkila S, Postila PA, Rissanen S, Juhola H, Vattulainen I, Róg T. Calcium Assists Dopamine Release by Preventing Aggregation on the Inner Leaflet of Presynaptic Vesicles. ACS Chemical Neuroscience. 2017 Jun 21;8(6):1242-1250. https://doi.org/10.1021/acschemneuro.6b00395

Author

Mokkila, Sini ; Postila, Pekka A. ; Rissanen, Sami ; Juhola, Hanna ; Vattulainen, Ilpo ; Róg, Tomasz. / Calcium Assists Dopamine Release by Preventing Aggregation on the Inner Leaflet of Presynaptic Vesicles. In: ACS Chemical Neuroscience. 2017 ; Vol. 8, No. 6. pp. 1242-1250.

Bibtex - Download

@article{4c36393787dc4d6d8c2cfbfa2450a1cf,
title = "Calcium Assists Dopamine Release by Preventing Aggregation on the Inner Leaflet of Presynaptic Vesicles",
abstract = "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.",
keywords = "binding free energy, dopamine, molecular dynamics simulations, neurotransmitter release, phosphatidylcholine, presynaptic vesicle, Synaptic neurotransmission",
author = "Sini Mokkila and Postila, {Pekka A.} and Sami Rissanen and Hanna Juhola and Ilpo Vattulainen and Tomasz R{\'o}g",
note = "INT=fys,{"}Mokkila, Sini{"} EXT={"}Postila, Pekka A.{"}",
year = "2017",
month = "6",
day = "21",
doi = "10.1021/acschemneuro.6b00395",
language = "English",
volume = "8",
pages = "1242--1250",
journal = "ACS Chemical Neuroscience",
issn = "1948-7193",
publisher = "American Chemical Society",
number = "6",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Calcium Assists Dopamine Release by Preventing Aggregation on the Inner Leaflet of Presynaptic Vesicles

AU - Mokkila, Sini

AU - Postila, Pekka A.

AU - Rissanen, Sami

AU - Juhola, Hanna

AU - Vattulainen, Ilpo

AU - Róg, Tomasz

N1 - INT=fys,"Mokkila, Sini" EXT="Postila, Pekka A."

PY - 2017/6/21

Y1 - 2017/6/21

N2 - 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.

AB - 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.

KW - binding free energy

KW - dopamine

KW - molecular dynamics simulations

KW - neurotransmitter release

KW - phosphatidylcholine

KW - presynaptic vesicle

KW - Synaptic neurotransmission

U2 - 10.1021/acschemneuro.6b00395

DO - 10.1021/acschemneuro.6b00395

M3 - Article

VL - 8

SP - 1242

EP - 1250

JO - ACS Chemical Neuroscience

JF - ACS Chemical Neuroscience

SN - 1948-7193

IS - 6

ER -