Key result
Mutating the β9-strand of the Kv11.1 channel cNBH domain to alanines (AAA mutant) significantly destabilized the open state, shifting the voltage dependence of deactivation by +37.9 mV compared to wild-type channels.
Population
Kv11.1 potassium channels (preclinical model)
Comparison
Mutations to residues in the C-terminal… vs Wild-type Kv11.1 channels
Design
Preclinical
Authors
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Does not yet alter LQT2 management; extends structural understanding of Kv11.1 gating in vitro.
Mean Difference: 37.9
Absolute Event Rate: -23.4% vs -61.3%
The C-terminal β9-strand of the cNBH domain in Kv11.1 channels is crucial for stabilizing activated states and ensuring proper channel assembly and trafficking, providing mechanistic insight into long QT syndrome type 2.
Ng et al. (2013) studied Long QT syndrome type 2 (LQT2) mechanisms. β9-strand mutations (e.g., AAA mutant) vs. Wild-type Kv11.1 channels was evaluated on Voltage dependence of deactivation (V0.5) (37.9 mV depolarizing shift). Mutating the β9-strand of the Kv11.1 channel cNBH domain to alanines (AAA mutant) significantly destabilized the open state, shifting the voltage dependence of deactivation by +37.9 mV compared to wild-type channels.
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