SYNKOVÁ, Iva, Markéta BÉBAROVÁ, Irena ANDRŠOVÁ, Larisa CHMELIKOVA, Olga ŠVECOVÁ, Jan HOSEK, Michal PÁSEK, Pavel VÍT, Iveta VALÁŠKOVÁ, Renata GAILLYOVÁ, Rostislav NAVRATIL a Tomáš NOVOTNÝ. Long-QT founder variant T309I-Kv7.1 with dominant negative pattern may predispose delayed afterdepolarizations under β-adrenergic stimulation. Nature Scientific Reports. London: NATURE RESEARCH, 2021, roč. 11, č. 1, s. 1-13. ISSN 2045-2322. Dostupné z: https://dx.doi.org/10.1038/s41598-021-81670-1. |
Další formáty:
BibTeX
LaTeX
RIS
@article{1765769, author = {Synková, Iva and Bébarová, Markéta and Andršová, Irena and Chmelikova, Larisa and Švecová, Olga and Hosek, Jan and Pásek, Michal and Vít, Pavel and Valášková, Iveta and Gaillyová, Renata and Navratil, Rostislav and Novotný, Tomáš}, article_location = {London}, article_number = {1}, doi = {http://dx.doi.org/10.1038/s41598-021-81670-1}, keywords = {Long-QT founder variant T309I-Kv7.1; afterdepolarizations; β-adrenergic stimulation}, language = {eng}, issn = {2045-2322}, journal = {Nature Scientific Reports}, title = {Long-QT founder variant T309I-Kv7.1 with dominant negative pattern may predispose delayed afterdepolarizations under β-adrenergic stimulation}, url = {https://www.nature.com/articles/s41598-021-81670-1.pdf}, volume = {11}, year = {2021} }
TY - JOUR ID - 1765769 AU - Synková, Iva - Bébarová, Markéta - Andršová, Irena - Chmelikova, Larisa - Švecová, Olga - Hosek, Jan - Pásek, Michal - Vít, Pavel - Valášková, Iveta - Gaillyová, Renata - Navratil, Rostislav - Novotný, Tomáš PY - 2021 TI - Long-QT founder variant T309I-Kv7.1 with dominant negative pattern may predispose delayed afterdepolarizations under β-adrenergic stimulation JF - Nature Scientific Reports VL - 11 IS - 1 SP - 1-13 EP - 1-13 PB - NATURE RESEARCH SN - 20452322 KW - Long-QT founder variant T309I-Kv7.1 KW - afterdepolarizations KW - β-adrenergic stimulation UR - https://www.nature.com/articles/s41598-021-81670-1.pdf N2 - The variant c.926C > T (p.T309I) in KCNQ1 gene was identified in 10 putatively unrelated Czech families with long QT syndrome (LQTS). Mutation carriers (24 heterozygous individuals) were more symptomatic compared to their non-affected relatives (17 individuals). The carriers showed a mild LQTS phenotype including a longer QTc interval at rest (466 ± 24 ms vs. 418 ± 20 ms) and after exercise (508 ± 32 ms vs. 417 ± 24 ms), 4 syncopes and 2 aborted cardiac arrests. The same haplotype associated with the c.926C > T variant was identified in all probands. Using the whole cell patch clamp technique and confocal microscopy, a complete loss of channel function was revealed in the homozygous setting, caused by an impaired channel trafficking. Dominant negativity with preserved reactivity to β-adrenergic stimulation was apparent in the heterozygous setting. In simulations on a human ventricular cell model, the dysfunction resulted in delayed afterdepolarizations (DADs) and premature action potentials under β-adrenergic stimulation that could be prevented by a slight inhibition of calcium current. We conclude that the KCNQ1 variant c.926C > T is the first identified LQTS-related founder mutation in Central Europe. The dominant negative channel dysfunction may lead to DADs under β-adrenergic stimulation. Inhibition of calcium current could be possible therapeutic strategy in LQTS1 patients refractory to β-blocker therapy. ER -
SYNKOVÁ, Iva, Markéta BÉBAROVÁ, Irena ANDRŠOVÁ, Larisa CHMELIKOVA, Olga ŠVECOVÁ, Jan HOSEK, Michal PÁSEK, Pavel VÍT, Iveta VALÁŠKOVÁ, Renata GAILLYOVÁ, Rostislav NAVRATIL a Tomáš NOVOTNÝ. Long-QT founder variant T309I-Kv7.1 with dominant negative pattern may predispose delayed afterdepolarizations under β-adrenergic stimulation. \textit{Nature Scientific Reports}. London: NATURE RESEARCH, 2021, roč.~11, č.~1, s.~1-13. ISSN~2045-2322. Dostupné z: https://dx.doi.org/10.1038/s41598-021-81670-1.
|