Properties of a novel GABAA receptor γ2 subunit mutation associated with seizures.

We recently identified a novel missense mutation of the γ(2) subunit at position 40 with serine (N40S) of the GABA(A) receptor from a patient with epilepsy. Here, we report properties of the mutant receptor using the whole cell patch clamp technique. The Hill coefficient for the N40S receptor was greater than for the wild-type (WT) receptor, while the EC50 and kinetics did not differ. Furthermore, the effects of diazepam, Zn(2+), bicuculline, and pH were indistinguishable between WT and N40S receptors. These results suggest that the changes in the steepness of the concentration-response relationship for GABA in the N40S receptor may trigger epilepsy.