KCNQ2 and KCNQ3 K+ channel subunits underlie the muscarinic-regulated K+ current 
(I(KM)), a widespread regulator of neuronal excitability. Mutations in KCNQ2- or 
KCNQ3-encoding genes cause benign familiar neonatal convulsions (BFNCs), a rare 
autosomal-dominant idiopathic epilepsy of the newborn. In the present study, we 
have investigated, by means of electrophysiological, biochemical, and 
immunocytochemical techniques in transiently transfected cells, the consequences 
prompted by a BFNC-causing 1-bp deletion (2043deltaT) in the KCNQ2 gene; this 
frameshift mutation caused the substitution of the last 163 amino acids of the 
KCNQ2 C terminus and the extension of the subunit by additional 56 residues. The 
2043deltaT mutation abolished voltage-gated K+ currents produced upon homomeric 
expression of KCNQ2 subunits, dramatically reduced the steady-state cellular 
levels of KCNQ2 subunits, and prevented their delivery to the plasma membrane. 
Metabolic labeling experiments revealed that mutant KCNQ2 subunits underwent 
faster degradation; 10-h treatment with the proteasomal inhibitor MG132 (20 
microm) at least partially reversed such enhanced degradation. Co-expression 
with KCNQ3 subunits reduced the degradation rate of mutant KCNQ2 subunits and 
led to their expression on the plasma membrane. Finally, co-expression of KCNQ2 
2043deltaT together with KCNQ3 subunits generated functional voltage-gated K+ 
currents having pharmacological and biophysical properties of heteromeric 
channels. Collectively, the present results suggest that mutation-induced 
reduced stability of KCNQ2 subunits may cause epilepsy in neonates.