The ability of KCNQ (Kv7) channels to form hetero-oligomers is of high physiological importance, since heteromers of KCNQ3 with KCNQ2 or KCNQ5 underlie the neuronal M-current, which modulates neuronal excitability. Mutations in either KCNQ2 or KCNQ3 underlie benign familial neonatal convulsions (BFNC) an inherited epilepsy. The corresponding proteins are co-expressed in broad regions of the brain and associate to heteromeric K+ channels. Co-expression of both subunits gave rise to currents that are at least tenfold larger than those of the respective homomeric channels. We have shown that the current augmentation is primarily due to an increased surface expression of active channels. By using a chimeric strategy, we have identified a subunit interaction (si) domain within the carboxyterminus that determines the subunit-specific assembly of KCNQ2 and KCNQ3. Within this si domain, there are two motifs, which comprise about 30 amino acids residues each that exhibit a high probability for coiled-coil formation. A detailed analysis of the two predicted coiled-coil structures suggest that the first highly conserved coiled-coil is necessary for the formation of homomeric and heteromeric KCNQ2/KCNQ3 channels, whereas both second coiled-coil structures are important for an efficient transport of heteromeric channels to the plasma membrane.