The NALCN channel complex is voltage sensitive and directly modulated by extracellular calcium

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

The NALCN channel complex is voltage sensitive and directly modulated by extracellular calcium. / Chua, H. C.; Wulf, M.; Weidling, C.; Rasmussen, L. P.; Pless, S. A.

In: Science Advances, Vol. 6, No. 17, aaz3154, 04.2020.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Chua, HC, Wulf, M, Weidling, C, Rasmussen, LP & Pless, SA 2020, 'The NALCN channel complex is voltage sensitive and directly modulated by extracellular calcium', Science Advances, vol. 6, no. 17, aaz3154. https://doi.org/10.1126/sciadv.aaz3154

APA

Chua, H. C., Wulf, M., Weidling, C., Rasmussen, L. P., & Pless, S. A. (2020). The NALCN channel complex is voltage sensitive and directly modulated by extracellular calcium. Science Advances, 6(17), [aaz3154]. https://doi.org/10.1126/sciadv.aaz3154

Vancouver

Chua HC, Wulf M, Weidling C, Rasmussen LP, Pless SA. The NALCN channel complex is voltage sensitive and directly modulated by extracellular calcium. Science Advances. 2020 Apr;6(17). aaz3154. https://doi.org/10.1126/sciadv.aaz3154

Author

Chua, H. C. ; Wulf, M. ; Weidling, C. ; Rasmussen, L. P. ; Pless, S. A. / The NALCN channel complex is voltage sensitive and directly modulated by extracellular calcium. In: Science Advances. 2020 ; Vol. 6, No. 17.

Bibtex

@article{a7191007146d4fcea65cfefd68d2d4a6,
title = "The NALCN channel complex is voltage sensitive and directly modulated by extracellular calcium",
abstract = "The sodium leak channel (NALCN) is essential for survival in mammals: NALCN mutations are life-threatening in humans and knockout is lethal in mice. However, the basic functional and pharmacological properties of NALCN have remained elusive. Here, we found that robust function of NALCN in heterologous systems requires co-expression of UNC79, UNC80, and FAM155A. The resulting NALCN channel complex is constitutively active and conducts monovalent cations but is blocked by physiological concentrations of extracellular divalent cations. Our data support the notion that NALCN is directly responsible for the increased excitability observed in a variety of neurons in reduced extracellular Ca2+. Despite the smaller number of voltage-sensing residues in NALCN, the constitutive activity is modulated by voltage, suggesting that voltage-sensing domains can give rise to a broader range of gating phenotypes than previously anticipated. Our work points toward formerly unknown contributions of NALCN to neuronal excitability and opens avenues for pharmacological targeting.",
author = "Chua, {H. C.} and M. Wulf and C. Weidling and Rasmussen, {L. P.} and Pless, {S. A.}",
year = "2020",
month = apr,
doi = "10.1126/sciadv.aaz3154",
language = "English",
volume = "6",
journal = "Science advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "17",

}

RIS

TY - JOUR

T1 - The NALCN channel complex is voltage sensitive and directly modulated by extracellular calcium

AU - Chua, H. C.

AU - Wulf, M.

AU - Weidling, C.

AU - Rasmussen, L. P.

AU - Pless, S. A.

PY - 2020/4

Y1 - 2020/4

N2 - The sodium leak channel (NALCN) is essential for survival in mammals: NALCN mutations are life-threatening in humans and knockout is lethal in mice. However, the basic functional and pharmacological properties of NALCN have remained elusive. Here, we found that robust function of NALCN in heterologous systems requires co-expression of UNC79, UNC80, and FAM155A. The resulting NALCN channel complex is constitutively active and conducts monovalent cations but is blocked by physiological concentrations of extracellular divalent cations. Our data support the notion that NALCN is directly responsible for the increased excitability observed in a variety of neurons in reduced extracellular Ca2+. Despite the smaller number of voltage-sensing residues in NALCN, the constitutive activity is modulated by voltage, suggesting that voltage-sensing domains can give rise to a broader range of gating phenotypes than previously anticipated. Our work points toward formerly unknown contributions of NALCN to neuronal excitability and opens avenues for pharmacological targeting.

AB - The sodium leak channel (NALCN) is essential for survival in mammals: NALCN mutations are life-threatening in humans and knockout is lethal in mice. However, the basic functional and pharmacological properties of NALCN have remained elusive. Here, we found that robust function of NALCN in heterologous systems requires co-expression of UNC79, UNC80, and FAM155A. The resulting NALCN channel complex is constitutively active and conducts monovalent cations but is blocked by physiological concentrations of extracellular divalent cations. Our data support the notion that NALCN is directly responsible for the increased excitability observed in a variety of neurons in reduced extracellular Ca2+. Despite the smaller number of voltage-sensing residues in NALCN, the constitutive activity is modulated by voltage, suggesting that voltage-sensing domains can give rise to a broader range of gating phenotypes than previously anticipated. Our work points toward formerly unknown contributions of NALCN to neuronal excitability and opens avenues for pharmacological targeting.

U2 - 10.1126/sciadv.aaz3154

DO - 10.1126/sciadv.aaz3154

M3 - Journal article

C2 - 32494638

AN - SCOPUS:85084653815

VL - 6

JO - Science advances

JF - Science advances

SN - 2375-2548

IS - 17

M1 - aaz3154

ER -

ID: 245323777