Key result
Bulkier hydrophobic Ala653 substitutions shift hERG1 activation by ~54 mV, while charged residues prevent closure.
Population
Xenopus oocytes expressing mutant hERG1 channels
Comparison
Substitution of conserved Ala653 with other… vs Wild-type hERG1 channels
Design
Preclinical
Authors
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Ala653 critical for hERG gating in animal models; leaves open relevance to human arrhythmia risk.
The conserved Ala653 residue in the hERG1 channel is essential for normal voltage-dependent gating and channel closure.
Brown et al. (2008) studied hERG1 K+ channel function. Substitution of Ala653 with other amino acids vs. Wild-type channels was evaluated on Voltage dependent activation and channel deactivation. Substitution of Ala653 with bulkier hydrophobic residues shifted voltage-dependent activation by -54 mV (for A653V), while charged residues prevented channel closure.
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