Figure 1.

Topological representation of voltage-gated K⁺ (K_v), Na⁺ (Na_v) and Ca²⁺ (Ca_v) channels with related neuronal diseases. Na_v channels are formed by a single polypeptide that contains four domains (I-IV), each with six transmembrane segments (S₁–S₆). β-subunits are single transmembrane proteins that co-assembles with the Na_v α-subunit. Ca_v channels show a similar topology to Na_v channels in their α-subunits, but can be associated with four different auxiliary subunits: the α₂/δ-complex, linked by disulfide bridges, an intracellular β-subunit, and an occasional γ-subunit with four transmembrane segments. Abbreviations: GEFS⁺, Generalized Epilepsy with Febrile Seizures plus; SMEI, Severe Myoclonic Epilepsy of Infancy; FHM1-3, Familial Hemiplegic Migraine type 1-3, respectively; BFNS, Benign Familial Neonatal Seizures; BFNIS, Benign Familial Neonatal-Infantile Seizures; EE, Epileptic Encephalopathy; PE, Primary Erythermalgia; PEPD, Paroxysmal Extreme Pain Disorder; CIP, Congenital Insensitivity to Pain; FEPS2-3, Familial Episodic Pain Syndrome type 2-3, respectively; HSAN7, Hereditary Sensory and Autonomic Neuropathy type 7; EA1-2, Episodic Ataxia type 1-2, respectively; SCA6-13, Spinocerebellar Ataxia type 6-13, respectively; PME, Progressive Myoclonus Epilepsy; CDSRR, Cone Dystrophy with Supernormal Rod Electroretinogram.