Informace o publikaci
Functional analysis of mutant IKs channels associated with long QT syndrome type 1
| Autoři | |
|---|---|
| Rok publikování | 2018 |
| Druh | Konferenční abstrakty |
| Fakulta / Pracoviště MU | |
| Citace | |
| Popis | Long QT syndrome type 1 (LQT1) is an inherited arrhythmogenic syndrome caused by mostly heterozygous loss-of-function mutations in the KCNQ1 gene encoding structure of the alpha-subunit (Kv7.1 protein) of slow delayed rectifier potassium current (IKs), an important repolarizing current, especially during increased sympathetic stimulation. We aimed to analyse functional impact of two Kv7.1 mutations that have not been studied so far, namely P-loop mutation T309I and C-terminal mutation R562S. Measurements by the whole cell patch clamp technique were performed at 37?degrees of C on wild-type (WT) and mutant human IKs channels transiently expressed on Chinese hamster ovary cells. Confocal microscopy was used to reveal cell localization of the channels. T309I mutation resulted in a complete loss of function due to absent cell membrane expression of the channels as proved by confocal microscopy. When WT and mutant subunits were coexpressed (1:1), haploinsufficiency character of the response was apparent with the average current at 0 mV decreased by about 55 %. A slight rightward shift and deceleration of activation of the current was also apparent. R562S mutation resulted at 0 mV in a decreased current (by about 49 %) with delayed and rightward shifted activation. Cotransfection of WT and R562S has not been tested so far. Our data revealed dysfunctional channels in both tested mutations. The dysfunction seemed to be mild in the case of R562S mutation. Hence, the pathogenic character of this mutation remains to be further proved. |
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