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@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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