Mutations in the Kv1.5 channel gene KCNA5 in cardiac arrest patients.

Nathalie H Nielsen; Bo G Winkel; Jørgen K Kanters; Nicole Schmitt; Jacob Hofman-Bang; Henrik S Jensen; Bo H Bentzen; Bjarne Sigurd; Lars Allan Larsen; Paal S Andersen; Keld Kjeldsen; Morten Grunnet; Michael Christiansen; Søren-Peter Olesen; Stig Haunsø

doi:10.1016/j.bbrc.2007.01.048

Mutations in the Kv1.5 channel gene KCNA5 in cardiac arrest patients.

Nathalie H Nielsen, Bo G Winkel, Jørgen K Kanters, Nicole Schmitt, Jacob Hofman-Bang, Henrik S Jensen, Bo H Bentzen, Bjarne Sigurd, Lars Allan Larsen, Paal S Andersen, Keld Kjeldsen, Morten Grunnet, Michael Christiansen, Søren-Peter Olesen, Stig Haunsø

22 Citations (Scopus)

Abstract

Mutations in one of the ion channels shaping the cardiac action potential can lead to action potential prolongation. However, only in a minority of cardiac arrest cases mutations in the known arrhythmia-related genes can be identified. In two patients with arrhythmia and cardiac arrest, we identified the point mutations P91L and E33V in the KCNA5 gene encoding the Kv1.5 potassium channel that has not previously been associated with arrhythmia. We functionally characterized the mutations in HEK293 cells. The mutated channels behaved similarly to the wild-type with respect to biophysical characteristics and drug sensitivity. Both patients also carried a D85N polymorphism in KCNE1, which was neither found to influence the Kv1.5 nor the Kv7.1 channel activity. We conclude that although the two N-terminal Kv1.5 mutations did not show any apparent electrophysiological phenotype, it is possible that they may influence other cellular mechanisms responsible for proper electrical behaviour of native cardiomyocytes.
Udgivelsesdato: 2007-Mar-16

Original language	English
Journal	Biochemical and Biophysical Research Communications
Volume	354
Issue number	3
Pages (from-to)	776-82
Number of pages	6
ISSN	0006-291X
DOIs	https://doi.org/10.1016/j.bbrc.2007.01.048
Publication status	Published - 2007

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10.1016/j.bbrc.2007.01.048

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Nielsen, N. H., Winkel, B. G., Kanters, J. K., Schmitt, N., Hofman-Bang, J., Jensen, H. S., Bentzen, B. H., Sigurd, B., Larsen, L. A., Andersen, P. S., Kjeldsen, K., Grunnet, M., Christiansen, M., Olesen, S-P., & Haunsø, S. (2007). Mutations in the Kv1.5 channel gene KCNA5 in cardiac arrest patients. Biochemical and Biophysical Research Communications, 354(3), 776-82. https://doi.org/10.1016/j.bbrc.2007.01.048

Nielsen, NH, Winkel, BG, Kanters, JK , Schmitt, N, Hofman-Bang, J, Jensen, HS, Bentzen, BH, Sigurd, B, Larsen, LA, Andersen, PS, Kjeldsen, K, Grunnet, M, Christiansen, M, Olesen, S-P & Haunsø, S 2007, 'Mutations in the Kv1.5 channel gene KCNA5 in cardiac arrest patients.', Biochemical and Biophysical Research Communications, vol. 354, no. 3, pp. 776-82. https://doi.org/10.1016/j.bbrc.2007.01.048

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title = "Mutations in the Kv1.5 channel gene KCNA5 in cardiac arrest patients.",

abstract = "Mutations in one of the ion channels shaping the cardiac action potential can lead to action potential prolongation. However, only in a minority of cardiac arrest cases mutations in the known arrhythmia-related genes can be identified. In two patients with arrhythmia and cardiac arrest, we identified the point mutations P91L and E33V in the KCNA5 gene encoding the Kv1.5 potassium channel that has not previously been associated with arrhythmia. We functionally characterized the mutations in HEK293 cells. The mutated channels behaved similarly to the wild-type with respect to biophysical characteristics and drug sensitivity. Both patients also carried a D85N polymorphism in KCNE1, which was neither found to influence the Kv1.5 nor the Kv7.1 channel activity. We conclude that although the two N-terminal Kv1.5 mutations did not show any apparent electrophysiological phenotype, it is possible that they may influence other cellular mechanisms responsible for proper electrical behaviour of native cardiomyocytes. Udgivelsesdato: 2007-Mar-16",

author = "Nielsen, {Nathalie H} and Winkel, {Bo G} and Kanters, {J{\o}rgen K} and Nicole Schmitt and Jacob Hofman-Bang and Jensen, {Henrik S} and Bentzen, {Bo H} and Bjarne Sigurd and Larsen, {Lars Allan} and Andersen, {Paal S} and Keld Kjeldsen and Morten Grunnet and Michael Christiansen and S{\o}ren-Peter Olesen and Stig Hauns{\o}",

note = "Keywords: Cells, Cultured; Child; Cloning, Molecular; Electrophysiology; Female; Heart Arrest; Humans; Kv1.5 Potassium Channel; Male; Middle Aged; Mutation; Myocytes, Cardiac; Phenotype; Potassium Channels, Voltage-Gated; Time Factors",

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T1 - Mutations in the Kv1.5 channel gene KCNA5 in cardiac arrest patients.

AU - Nielsen, Nathalie H

AU - Winkel, Bo G

AU - Kanters, Jørgen K

AU - Schmitt, Nicole

AU - Hofman-Bang, Jacob

AU - Jensen, Henrik S

AU - Bentzen, Bo H

AU - Sigurd, Bjarne

AU - Larsen, Lars Allan

AU - Andersen, Paal S

AU - Kjeldsen, Keld

AU - Grunnet, Morten

AU - Christiansen, Michael

AU - Olesen, Søren-Peter

AU - Haunsø, Stig

N1 - Keywords: Cells, Cultured; Child; Cloning, Molecular; Electrophysiology; Female; Heart Arrest; Humans; Kv1.5 Potassium Channel; Male; Middle Aged; Mutation; Myocytes, Cardiac; Phenotype; Potassium Channels, Voltage-Gated; Time Factors

PY - 2007

Y1 - 2007

N2 - Mutations in one of the ion channels shaping the cardiac action potential can lead to action potential prolongation. However, only in a minority of cardiac arrest cases mutations in the known arrhythmia-related genes can be identified. In two patients with arrhythmia and cardiac arrest, we identified the point mutations P91L and E33V in the KCNA5 gene encoding the Kv1.5 potassium channel that has not previously been associated with arrhythmia. We functionally characterized the mutations in HEK293 cells. The mutated channels behaved similarly to the wild-type with respect to biophysical characteristics and drug sensitivity. Both patients also carried a D85N polymorphism in KCNE1, which was neither found to influence the Kv1.5 nor the Kv7.1 channel activity. We conclude that although the two N-terminal Kv1.5 mutations did not show any apparent electrophysiological phenotype, it is possible that they may influence other cellular mechanisms responsible for proper electrical behaviour of native cardiomyocytes. Udgivelsesdato: 2007-Mar-16

AB - Mutations in one of the ion channels shaping the cardiac action potential can lead to action potential prolongation. However, only in a minority of cardiac arrest cases mutations in the known arrhythmia-related genes can be identified. In two patients with arrhythmia and cardiac arrest, we identified the point mutations P91L and E33V in the KCNA5 gene encoding the Kv1.5 potassium channel that has not previously been associated with arrhythmia. We functionally characterized the mutations in HEK293 cells. The mutated channels behaved similarly to the wild-type with respect to biophysical characteristics and drug sensitivity. Both patients also carried a D85N polymorphism in KCNE1, which was neither found to influence the Kv1.5 nor the Kv7.1 channel activity. We conclude that although the two N-terminal Kv1.5 mutations did not show any apparent electrophysiological phenotype, it is possible that they may influence other cellular mechanisms responsible for proper electrical behaviour of native cardiomyocytes. Udgivelsesdato: 2007-Mar-16

U2 - 10.1016/j.bbrc.2007.01.048

DO - 10.1016/j.bbrc.2007.01.048

M3 - Journal article

C2 - 17266934

SN - 0006-291X

VL - 354

SP - 776

EP - 782

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 3

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