Impaired Adrenergic/Protein Kinase A Response of Slow Delayed
Rectifier Potassium Channels as a Long QT Syndrome Motif:
Importance and Unknowns

J 2019

Impaired Adrenergic/Protein Kinase A Response of Slow Delayed Rectifier Potassium Channels as a Long QT Syndrome Motif: Importance and Unknowns

POLICAROVÁ, Marcela, Tomáš NOVOTNÝ and Markéta BÉBAROVÁ

Basic information

Original name

Impaired Adrenergic/Protein Kinase A Response of Slow Delayed Rectifier Potassium Channels as a Long QT Syndrome Motif: Importance and Unknowns

Authors

POLICAROVÁ, Marcela (203 Czech Republic, belonging to the institution), Tomáš NOVOTNÝ (203 Czech Republic, belonging to the institution) and Markéta BÉBAROVÁ (203 Czech Republic, guarantor, belonging to the institution)

Edition

Canadian Journal of Cardiology, New York, Elsevier Science Ltd. 2019, 0828-282X

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30201 Cardiac and Cardiovascular systems

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 5.234

RIV identification code

RIV/00216224:14110/19:00108462

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1016/j.cjca.2018.11.012

UT WoS

000462763000022

Keywords in English

Impaired Adrenergic/Protein Kinase

Abstract

V originále

The slow delayed rectifier potassium current (I-Ks) significantly contributes to cardiac repolarization under specific conditions, particularly at stimulation by the protein kinase A (PKA) during increased sympathetic tone. Impaired PKA-mediated stimulation of I-Ks channels may considerably aggravate dysfunction of the channels induced by mutations in the KCNQ1 gene that encodes the structure of the alpha-subunit of I-Ks channels. These mutations are associated with several subtypes of inherited arrhythmias, mainly long QT syndrome type 1, less commonly short QT syndrome type 2, and atrial fibrillation. The impaired PKA reactivity of I-Ks channels may significantly increase the risk of arrhythmia in these patients. Unfortunately, only approximately 2.7% of the KCNQ1 variants identified as putatively clinically significant have been studied with respect to this problem. This review summarizes the current knowledge in the field to stress the importance of the PKA-mediated regulation of I-Ks channels, and to appeal for further analysis of this regulation in KCNQ1 mutations associated with inherited arrhythmogenic syndromes. On the basis of the facts summarized in our review, we suggest several new regions of the alpha-subunit of the I-Ks channels as potential contributors to PKA stimulation, namely the S4 and S5 segments, and the S2-S3 and S4-S5 linkers. Deeper knowledge of mechanisms of the impaired PKA response in mutated I-Ks channels may help to better understand this regulation, and may improve risk stratification and management of patients suffering from related pathologies.

Links

NV16-30571A, research and development project

Name: Klinický význam a elektrofyziologické zhodnocení mutace c.926C>T genu KCNQ1 (p.T309I) jako možné „founder mutation“ syndromu dlouhého intervalu QT

Citovat

POLICAROVÁ, Marcela, Tomáš NOVOTNÝ and Markéta BÉBAROVÁ. Impaired Adrenergic/Protein Kinase A Response of Slow Delayed Rectifier Potassium Channels as a Long QT Syndrome Motif: Importance and Unknowns. Canadian Journal of Cardiology. New York: Elsevier Science Ltd., 2019, vol. 35, No 4, p. 511-522. ISSN 0828-282X. Available from: https://dx.doi.org/10.1016/j.cjca.2018.11.012.

@article{1522603,
   author = {Policarová, Marcela and Novotný, Tomáš and Bébarová, Markéta},
   article_location = {New York},
   article_number = {4},
   doi = {http://dx.doi.org/10.1016/j.cjca.2018.11.012},
   keywords = {Impaired Adrenergic/Protein Kinase},
   language = {eng},
   issn = {0828-282X},
   journal = {Canadian Journal of Cardiology},
   title = {Impaired Adrenergic/Protein Kinase A Response of Slow Delayed Rectifier Potassium Channels as a Long QT Syndrome Motif: Importance and Unknowns},
   url = {http://dx.doi.org/10.1016/j.cjca.2018.11.012},
   volume = {35},
   year = {2019}
}

TY  - JOUR
ID  - 1522603
AU  - Policarová, Marcela - Novotný, Tomáš - Bébarová, Markéta
PY  - 2019
TI  - Impaired Adrenergic/Protein Kinase A Response of Slow Delayed Rectifier Potassium Channels as a Long QT Syndrome Motif: Importance and Unknowns
JF  - Canadian Journal of Cardiology
VL  - 35
IS  - 4
SP  - 511-522
EP  - 511-522
PB  - Elsevier Science Ltd.
SN  - 0828282X
KW  - Impaired Adrenergic/Protein Kinase
UR  - http://dx.doi.org/10.1016/j.cjca.2018.11.012
L2  - http://dx.doi.org/10.1016/j.cjca.2018.11.012
N2  - The slow delayed rectifier potassium current (I-Ks) significantly contributes to cardiac repolarization under specific conditions, particularly at stimulation by the protein kinase A (PKA) during increased sympathetic tone. Impaired PKA-mediated stimulation of I-Ks channels may considerably aggravate dysfunction of the channels induced by mutations in the KCNQ1 gene that encodes the structure of the alpha-subunit of I-Ks channels. These mutations are associated with several subtypes of inherited arrhythmias, mainly long QT syndrome type 1, less commonly short QT syndrome type 2, and atrial fibrillation. The impaired PKA reactivity of I-Ks channels may significantly increase the risk of arrhythmia in these patients. Unfortunately, only approximately 2.7% of the KCNQ1 variants identified as putatively clinically significant have been studied with respect to this problem. This review summarizes the current knowledge in the field to stress the importance of the PKA-mediated regulation of I-Ks channels, and to appeal for further analysis of this regulation in KCNQ1 mutations associated with inherited arrhythmogenic syndromes. On the basis of the facts summarized in our review, we suggest several new regions of the alpha-subunit of the I-Ks channels as potential contributors to PKA stimulation, namely the S4 and S5 segments, and the S2-S3 and S4-S5 linkers. Deeper knowledge of mechanisms of the impaired PKA response in mutated I-Ks channels may help to better understand this regulation, and may improve risk stratification and management of patients suffering from related pathologies.
ER  -

POLICAROVÁ, Marcela, Tomáš NOVOTNÝ and Markéta BÉBAROVÁ. Impaired Adrenergic/Protein Kinase A Response of Slow Delayed Rectifier Potassium Channels as a Long QT Syndrome Motif: Importance and Unknowns. \textit{Canadian Journal of Cardiology}. New York: Elsevier Science Ltd., 2019, vol.~35, No~4, p.~511-522. ISSN~0828-282X. Available from: https://dx.doi.org/10.1016/j.cjca.2018.11.012.

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