N-type Ca2+ channels carry the largest current: Implications for nanodomains and transmitter release

Alexander M. Weber; Fiona K. Wong; Adele R. Tufford; Lyanne C. Schlichter; Victor Matveev; Elise F. Stanley

doi:10.1038/nn.2657

N-type Ca²⁺ channels carry the largest current: Implications for nanodomains and transmitter release

Alexander M. Weber, Fiona K. Wong, Adele R. Tufford, Lyanne C. Schlichter, Victor Matveev, Elise F. Stanley

Mathematical Sciences

Research output: Contribution to journal › Article › peer-review

82 Scopus citations

Abstract

Presynaptic terminals favor intermediate-conductance Ca V₂.2 (N type) over high-conductance Ca _V 1 (L type) channels for single-channel, Ca²⁺ nanodomain-triggered synaptic vesicle fusion. However, the standard Ca _V 1>Ca _V 2>Ca _V 3 conductance hierarchy is based on recordings using nonphysiological divalent ion concentrations. We found that, with physiological Ca²⁺ gradients, the hierarchy was Ca _V 2.2>Ca _V 1>Ca _V 3. Mathematical modeling predicts that the Ca _V 2.2 Ca²⁺ nanodomain, which is ĝ̂1/425% more extensive than that generated by Ca _V 1, can activate a calcium-fusion sensor located on the proximal face of the synaptic vesicle.

Original language	English (US)
Pages (from-to)	1348-1350
Number of pages	3
Journal	Nature Neuroscience
Volume	13
Issue number	11
DOIs	https://doi.org/10.1038/nn.2657
State	Published - Nov 2010

All Science Journal Classification (ASJC) codes

General Neuroscience

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10.1038/nn.2657

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title = "N-type Ca2+ channels carry the largest current: Implications for nanodomains and transmitter release",

abstract = "Presynaptic terminals favor intermediate-conductance Ca V2.2 (N type) over high-conductance Ca V 1 (L type) channels for single-channel, Ca2+ nanodomain-triggered synaptic vesicle fusion. However, the standard Ca V 1>Ca V 2>Ca V 3 conductance hierarchy is based on recordings using nonphysiological divalent ion concentrations. We found that, with physiological Ca2+ gradients, the hierarchy was Ca V 2.2>Ca V 1>Ca V 3. Mathematical modeling predicts that the Ca V 2.2 Ca2+ nanodomain, which is {\^ĝ}1/425% more extensive than that generated by Ca V 1, can activate a calcium-fusion sensor located on the proximal face of the synaptic vesicle.",

author = "Weber, {Alexander M.} and Wong, {Fiona K.} and Tufford, {Adele R.} and Schlichter, {Lyanne C.} and Victor Matveev and Stanley, {Elise F.}",

note = "Funding Information: We thank G. Zamponi, P. Backx, S. Ikeda and A. Chan for critique of the manuscript, and Q. Li and X.P. Zhu for technical assistance. This work was supported primarily by Canadian Institutes for Health Research (MOP-86643) and a Canada Research Chair (E.F.S.). We also received funding from the Canadian Institutes for Health Research (MT-13657, L.C.S.), Ontario Graduate Scholarship (F.K.W.) and National Science Foundation (DMS-0817703, V.M.).",

year = "2010",

month = nov,

doi = "10.1038/nn.2657",

language = "English (US)",

volume = "13",

pages = "1348--1350",

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T2 - Implications for nanodomains and transmitter release

AU - Weber, Alexander M.

AU - Wong, Fiona K.

AU - Tufford, Adele R.

AU - Schlichter, Lyanne C.

AU - Matveev, Victor

AU - Stanley, Elise F.

N1 - Funding Information: We thank G. Zamponi, P. Backx, S. Ikeda and A. Chan for critique of the manuscript, and Q. Li and X.P. Zhu for technical assistance. This work was supported primarily by Canadian Institutes for Health Research (MOP-86643) and a Canada Research Chair (E.F.S.). We also received funding from the Canadian Institutes for Health Research (MT-13657, L.C.S.), Ontario Graduate Scholarship (F.K.W.) and National Science Foundation (DMS-0817703, V.M.).

PY - 2010/11

Y1 - 2010/11

N2 - Presynaptic terminals favor intermediate-conductance Ca V2.2 (N type) over high-conductance Ca V 1 (L type) channels for single-channel, Ca2+ nanodomain-triggered synaptic vesicle fusion. However, the standard Ca V 1>Ca V 2>Ca V 3 conductance hierarchy is based on recordings using nonphysiological divalent ion concentrations. We found that, with physiological Ca2+ gradients, the hierarchy was Ca V 2.2>Ca V 1>Ca V 3. Mathematical modeling predicts that the Ca V 2.2 Ca2+ nanodomain, which is ĝ̂1/425% more extensive than that generated by Ca V 1, can activate a calcium-fusion sensor located on the proximal face of the synaptic vesicle.

AB - Presynaptic terminals favor intermediate-conductance Ca V2.2 (N type) over high-conductance Ca V 1 (L type) channels for single-channel, Ca2+ nanodomain-triggered synaptic vesicle fusion. However, the standard Ca V 1>Ca V 2>Ca V 3 conductance hierarchy is based on recordings using nonphysiological divalent ion concentrations. We found that, with physiological Ca2+ gradients, the hierarchy was Ca V 2.2>Ca V 1>Ca V 3. Mathematical modeling predicts that the Ca V 2.2 Ca2+ nanodomain, which is ĝ̂1/425% more extensive than that generated by Ca V 1, can activate a calcium-fusion sensor located on the proximal face of the synaptic vesicle.

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N-type Ca²⁺ channels carry the largest current: Implications for nanodomains and transmitter release

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