N588K (SQTS)

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COMMENT
N588K was co-expressed with and without the ancillary subunit KCNE2 (MiRP1) in TSA201 cells by Brugada et al .
N588K/KCNE2 steady-state current continued to increase linearly well over +40 mV with a substantial loss of inward rectification typical of IKr. During action potential clamp experiments the wild-type showed typical hump-like waveform with slow activation kinetics and rapid increase during the repolarization phase of IKr (due to fast recovery from inactivation), N588K currents displayed a domelike configuration resulting in a much larger relative current during the initial phases of the action potential. These features suggest N588K causes a gain of function effect on the protein.
Additional experiments showed that mutated channels display a reduced sensitivity to the IKr blocker D-sotalol, indicating a poor potential therapeutic role of this drug.