Q147R (Familial atrial fibrillation - and Long QT syndrome)

- back to LQT1 or FAF mutations table - KCNQ1 cartoon - FAF synopsis

COMMENTS ON IN VITRO DATA

Heterologous expression in X. laevis oocytes and in mammalian cells (Lundby et al. 2007) was used to investigate the functional consequences of the mutation on the biophysical properties of Kv7.1 channel subunits in the absence and presence of accessory subunits. The Q147R mutation did not affect homomeric Kv7.1 currents. However, upon coexpression with KCNE1 or KCNE2 subunits, the mutated protein led to changes in channel properties compared to currents elicited by WT channel complexes. The steady-state currents recorded at the end of a 2-second depolarizing pulse to +60 mV were decreased by approximately 40% upon coexpression with KCNE1 and increased by approximately 50% upon coexpression with KCNE2 in both expression systems. The effects were slightly less pronounced in the mammalian expression system, possibly due to differences in regulatory pathways or the presence of endogenous channel subunits in the two systems. Coexpression with the regulatory β-subunit KCNE1 revealed a loss of function for the mutant, whereas coexpression with the β-subunit KCNE2 revealed a gain of function. That functional consequences of the mutation are seen only when the channel subunit is coexpressed with accessory subunits underscores the importance of the accessory KCNE subunits for the properties of Kv7.1-generated currents.