Impaired Adrenergic/Protein Kinase A Response of Slow Delayed Rectifier Potassium Channels as a Long QT Syndrome Motif: Importance and Unknowns
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F19%3A00108462" target="_blank" >RIV/00216224:14110/19:00108462 - isvavai.cz</a>
Alternative codes found
RIV/65269705:_____/19:00070886
Result on the web
<a href="http://dx.doi.org/10.1016/j.cjca.2018.11.012" target="_blank" >http://dx.doi.org/10.1016/j.cjca.2018.11.012</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.cjca.2018.11.012" target="_blank" >10.1016/j.cjca.2018.11.012</a>
Alternative languages
Result language
angličtina
Original language name
Impaired Adrenergic/Protein Kinase A Response of Slow Delayed Rectifier Potassium Channels as a Long QT Syndrome Motif: Importance and Unknowns
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30201 - Cardiac and Cardiovascular systems
Result continuities
Project
<a href="/en/project/NV16-30571A" target="_blank" >NV16-30571A: Clinical significance and electrophysiological evaluation of KCNQ1 gene mutation c.926C>T (p.T309I) as a possible long QT syndrome founder mutation</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Canadian Journal of Cardiology
ISSN
0828-282X
e-ISSN
1916-7075
Volume of the periodical
35
Issue of the periodical within the volume
4
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
511-522
UT code for WoS article
000462763000022
EID of the result in the Scopus database
2-s2.0-85063449079