Loss-of-activity-mutation in the cardiac chloride-bicarbonate exchanger AE3 causes short QT syndrome

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Loss-of-activity-mutation in the cardiac chloride-bicarbonate exchanger AE3 causes short QT syndrome. / Thorsen, Kasper; Dam, Vibeke S.; Kjaer-Sorensen, Kasper; Pedersen, Lisbeth N.; Skeberdis, V. Arvydas; Jurevicius, Jonas; Treinys, Rimantas; Petersen, Ida M. B. S.; Nielsen, Morten S.; Oxvig, Claus; Morth, J. Preben; Matchkov, Vladimir V.; Aalkjaer, Christian; Bundgaard, Henning; Jensen, Henrik K.

In: Nature Communications, Vol. 8, 1696, 22.11.2017.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Thorsen, K, Dam, VS, Kjaer-Sorensen, K, Pedersen, LN, Skeberdis, VA, Jurevicius, J, Treinys, R, Petersen, IMBS, Nielsen, MS, Oxvig, C, Morth, JP, Matchkov, VV, Aalkjaer, C, Bundgaard, H & Jensen, HK 2017, 'Loss-of-activity-mutation in the cardiac chloride-bicarbonate exchanger AE3 causes short QT syndrome', Nature Communications, vol. 8, 1696. https://doi.org/10.1038/s41467-017-01630-0

APA

Thorsen, K., Dam, V. S., Kjaer-Sorensen, K., Pedersen, L. N., Skeberdis, V. A., Jurevicius, J., ... Jensen, H. K. (2017). Loss-of-activity-mutation in the cardiac chloride-bicarbonate exchanger AE3 causes short QT syndrome. Nature Communications, 8, [1696]. https://doi.org/10.1038/s41467-017-01630-0

Vancouver

Thorsen K, Dam VS, Kjaer-Sorensen K, Pedersen LN, Skeberdis VA, Jurevicius J et al. Loss-of-activity-mutation in the cardiac chloride-bicarbonate exchanger AE3 causes short QT syndrome. Nature Communications. 2017 Nov 22;8. 1696. https://doi.org/10.1038/s41467-017-01630-0

Author

Thorsen, Kasper ; Dam, Vibeke S. ; Kjaer-Sorensen, Kasper ; Pedersen, Lisbeth N. ; Skeberdis, V. Arvydas ; Jurevicius, Jonas ; Treinys, Rimantas ; Petersen, Ida M. B. S. ; Nielsen, Morten S. ; Oxvig, Claus ; Morth, J. Preben ; Matchkov, Vladimir V. ; Aalkjaer, Christian ; Bundgaard, Henning ; Jensen, Henrik K. / Loss-of-activity-mutation in the cardiac chloride-bicarbonate exchanger AE3 causes short QT syndrome. In: Nature Communications. 2017 ; Vol. 8.

Bibtex

@article{ac1c9ae28cb9431e874a0a2e51268d08,
title = "Loss-of-activity-mutation in the cardiac chloride-bicarbonate exchanger AE3 causes short QT syndrome",
abstract = "Patients with short QT syndrome (SQTS) may present with syncope, ventricular fibrillation or sudden cardiac death. Six SQTS susceptibility genes, encoding cation channels, explain <25{\%} of SQTS cases. Here we identify a missense mutation in the anion exchanger (AE3)-encoding SLC4A3 gene in two unrelated families with SQTS. The mutation causes reduced surface expression of AE3 and reduced membrane bicarbonate transport. Slc4a3 knockdown in zebrafish causes increased cardiac pHi, short QTc, and reduced systolic duration, which is rescued by wildtype but not mutated SLC4A3. Mechanistic analyses suggest that an increase in pHi and decrease in [Cl−]i shortened the action potential duration. However, other mechanisms may also play a role. Altered anion transport represents a mechanism for development of arrhythmia and may provide new therapeutic possibilities.",
author = "Kasper Thorsen and Dam, {Vibeke S.} and Kasper Kjaer-Sorensen and Pedersen, {Lisbeth N.} and Skeberdis, {V. Arvydas} and Jonas Jurevicius and Rimantas Treinys and Petersen, {Ida M. B. S.} and Nielsen, {Morten S.} and Claus Oxvig and Morth, {J. Preben} and Matchkov, {Vladimir V.} and Christian Aalkjaer and Henning Bundgaard and Jensen, {Henrik K.}",
year = "2017",
month = "11",
day = "22",
doi = "10.1038/s41467-017-01630-0",
language = "English",
volume = "8",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Loss-of-activity-mutation in the cardiac chloride-bicarbonate exchanger AE3 causes short QT syndrome

AU - Thorsen, Kasper

AU - Dam, Vibeke S.

AU - Kjaer-Sorensen, Kasper

AU - Pedersen, Lisbeth N.

AU - Skeberdis, V. Arvydas

AU - Jurevicius, Jonas

AU - Treinys, Rimantas

AU - Petersen, Ida M. B. S.

AU - Nielsen, Morten S.

AU - Oxvig, Claus

AU - Morth, J. Preben

AU - Matchkov, Vladimir V.

AU - Aalkjaer, Christian

AU - Bundgaard, Henning

AU - Jensen, Henrik K.

PY - 2017/11/22

Y1 - 2017/11/22

N2 - Patients with short QT syndrome (SQTS) may present with syncope, ventricular fibrillation or sudden cardiac death. Six SQTS susceptibility genes, encoding cation channels, explain <25% of SQTS cases. Here we identify a missense mutation in the anion exchanger (AE3)-encoding SLC4A3 gene in two unrelated families with SQTS. The mutation causes reduced surface expression of AE3 and reduced membrane bicarbonate transport. Slc4a3 knockdown in zebrafish causes increased cardiac pHi, short QTc, and reduced systolic duration, which is rescued by wildtype but not mutated SLC4A3. Mechanistic analyses suggest that an increase in pHi and decrease in [Cl−]i shortened the action potential duration. However, other mechanisms may also play a role. Altered anion transport represents a mechanism for development of arrhythmia and may provide new therapeutic possibilities.

AB - Patients with short QT syndrome (SQTS) may present with syncope, ventricular fibrillation or sudden cardiac death. Six SQTS susceptibility genes, encoding cation channels, explain <25% of SQTS cases. Here we identify a missense mutation in the anion exchanger (AE3)-encoding SLC4A3 gene in two unrelated families with SQTS. The mutation causes reduced surface expression of AE3 and reduced membrane bicarbonate transport. Slc4a3 knockdown in zebrafish causes increased cardiac pHi, short QTc, and reduced systolic duration, which is rescued by wildtype but not mutated SLC4A3. Mechanistic analyses suggest that an increase in pHi and decrease in [Cl−]i shortened the action potential duration. However, other mechanisms may also play a role. Altered anion transport represents a mechanism for development of arrhythmia and may provide new therapeutic possibilities.

U2 - 10.1038/s41467-017-01630-0

DO - 10.1038/s41467-017-01630-0

M3 - Journal article

C2 - 29167417

VL - 8

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 1696

ER -

ID: 187290760