A561V (LQT-2)
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| Tail current @ 20mV | Shift in V1/2 of activation | Kinetic of activation | Slope of activation curve (k) | Expression System | Other | Reference |
|---|---|---|---|---|---|---|
| WT 167±123 nA |
WT -29±0.7mV |
N.S. | WT 8.7±0.2 mV |
Xenopus Oocytes | Co-expression of A561V with wild type resulted in a 57% reduction of current | Sanguinetti et al. in 1996 |
| AV No current |
AV -37±0.7 mV |
AV 7.9±0.2 mV |
no co-ex with beta1 | |||
| AV+WT 71±8 nA |
Negative | Faster |
N.S. : non different from WT;
COMMENT
The Alanine to Valine substitution at position 561 of the HERG channel
is one of the most "typical" LQT2 mutations and codon 561 is considered
a LQTS hot spot. This mutation affects the S5 transmembrane segment of
the KCNE2 encoded protein. T wave morphological abnormalities, with
notches and bi-phasic T waves in the precordial leads, are consistently
associated with this mutation. In vitro expression data show a dominant
effect on the wild type current, meaning that this mutation is
expressed in the membrane and functionally impairs the wild type
subunits.