Electrical hyperexcitability in the CNS can result in epileptical seizures. A specific form of epilepsy, called benign familial neonatal convulsions (BFNC), could be identified to originate from mutations in KCNQ2 (Kv7.2) and KCNQ3 (Kv7.3) K+ channel genes. Hence, drugs activating KCNQ (Kv7) channels could advantage the therapy of certain epilepsies. A compound specifically acting on KCNQ2-5 (Kv7.2-5) channels without affecting KCNQ1 is Retigabine whose anticonvulsant activity could be proved in animal models. Using a chimeric approach, a single tryptophane residue within the N-terminal part of the S5 segment was identified as being crucial for the mediation of the retigabine effect. Futhermore, it was shown that four retigabine binding sites must be existent in a tetramer to exert the activating retigabine effect. Besides, a single amino acid within the pore region was identified to modulate the retigabine sensitivity. Additionally, we could show that the surface expression of KCNQ3 could be dramatically improved by inserting a N-glycosylation site from KCNQ1, leading to an increase in maximal current without affecting retigabine sensitivity.