Y1795InsD (BS+LQTS)
- back to: BS table LQT3
table- SCN5A cartoon -
| Current Density | Shift in V1/2 of activation | Shift in V1/2 of inactivation | Kinetic of Inactivation | Recovery from Inactivation | I-sus | Expression System | Other | Reference |
|---|---|---|---|---|---|---|---|---|
| Time course of inactivation not different from wild type | Bezzina et al. 1999 | |||||||
| Ins
D: +8.1 mV |
Ins
D: -7.3 mV |
InsD: 1.2x@ -100mV |
significantly increase
|
|||||
| Negative | Slower |
N.S. : non different from WT
COMMENTS
At codon 1795 of the SCN5A protein two additional mutations have been reported
Y1795C, associated with a LQTS phenotype and Y1795H,
associated with a Brugada syndrome phenotype.
In a recent study, Veldkamp
et al. assessed the effect of 1795InsD in sinus node cells and confirmed
the presence of late sustained current (Ipst) and negative shift on inactivation.
In a computerized model of sinus node action potential a 10-mV shift decreased
sinus rate by decreasing diastolic depolarization rate, whereas Ipst decreased
sinus rate by AP prolongation, despite a concomitant increase in diastolic depolarization
rate. In combination, moderate Ipst (1% to 2%) and the shift reduced sinus rate
by 10%. An additional increase in Ipst could result in plateau oscillations
and failure to repolarize completely. These data suggest that the effects of
1795InsD on sinus node function may account for the bradycardia seen in LQT3
patients.