Vliv varianty S1021Qfs*98 v genu hERG na aktivaci a deaktivaci proteinu Kv11.1
| Title in English | Effect of S1021Qfs*98 variant in the hERG gene on activation and deactivation of Kv11.1 protein |
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| Year of publication | 2024 |
| Type | Conference abstract |
| MU Faculty or unit | |
| Citation | |
| Description | Introduction: The Kv11.1 protein encoded by the hERG gene forms a subunit of the potassium channel that contributes significantly to myocardial repolarization. The aim of this study is the functional characterization of two variants in the hERG gene, A228V and S1021Qfs*98, found in a proband with idiopathic ventricular fibrillation. Methods: measurements were performed by whole cell patch clamp method in voltage clamp mode at 37 °C on Chinese hamster ovary (CHO) cells transiently transfected with plasmids carrying the hERG gene without mutation (WT) and with the S1021Qfs*98 mutation. RESULTS: Activation of the channel affected by the mutation showed a 70% decrease in current compared with WT (at 0 mV: 219.4 pA for WT vs. 65.3 pA for S1021Qfs*98; P < 0.01, n = 17 and 18 for WT and S1021Qfs*98, respectively). However, there was no significant change in the voltage or time dependence of steady-state activation. The rate of deactivation also showed no significant change (at -90 mV: 122.1 ms in WT vs. 144.2 ms in S1021Qfs*98; P > 0.05, n = 15 and 16 in WT and S1021Qfs*98, respectively). Conclusion. The S1021Qfs*98-Kv11 variant. 1 caused a 70% decrease in potassium current compared to WT, but there were no significant changes in the time and voltage dependence of mutant channel activation and deactivation. As with other loss-of-function mutations in the hERG gene, which usually cause a delay in repolarization, the arrhythmogenic potential of the studied variant can be assumed. |
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