N629D
(LQT-2)
- back to mutations table - HERG cartoon -
| Tail current | Shift in V1/2 of activation | Slope of activation curve | Deactivation
(-80mV) * |
Expression System | Other | Reference |
|---|---|---|---|---|---|---|
| WT |
WT -26±7mV |
WT 9.0±0.6 mV |
WT 200±25 ms |
Xenopus Oocytes |
Analysis of reversal potential and replacement of Na with
NMG and K with Cs, showed that N629D channel is relatively nonselective
among cations
|
Lees-Miller 2000 |
| ND NEGATIVE tail currents |
ND -37±7 mV |
ND 8.0±1.0 mV |
ND 78±22 ms |
co-ex with WT | ||
| Negative | Faster | |||||
| This feature may indicate loss of potassium selectivity |
Similar data also @ -100mV
|
* Deactivation was fitted with a bi-exponential function but only the fast component has been reported. N.S. : non different from WT;
COMMENT
N629 lies in the pore region of the HERG channel. The two main consequences
of N629D mutation are a loss of C-type intactivation and cation selectivity.
Owtward tail currents (resulting from the recovery of inactivated channels during
repolarization) are eliminated, thus impairing the later phases of cardiac repolarization
and possibly confering susceptibility to cardiac arrhythmias.
A peculiar feature of this mutation is a loss of selectivity of K+
over Na+, manifesting with a inward Na+ current at membrane
potentials from -20mV to -70mV. &Thus, N629D replaces the WT outward repolarizing
tail current with an inward depolarizing sodium current, which is expected to
delay later stages of repolarization and contribute to arrhythmogenesis