title: Targeting BK (big potassium) channels in epilepsy.
abstract: BACKGROUND
  Epilepsies are disorders of neuronal excitability characterized by spontaneous and recurrent seizures. Ion channels are critical for regulating neuronal excitability and, therefore, can contribute significantly to epilepsy pathophysiology. In particular, large conductance, Ca2+-activated K+ (BKCa) channels play an important role in seizure etiology. These channels are activated by both membrane depolarization and increased intracellular Ca2+. This unique coupling of Ca2+ signaling to membrane depolarization is important in controlling neuronal hyperexcitability, as outward K+ current through BKCa channels hyperpolarizes neurons.
  
  
  METHODS
  BKCa channel structure-function and the role of these channels in epilepsy pathophysiology.
  
  
  CONCLUSIONS
  Loss-of-function BKCa channel mutations contribute to neuronal hyperexcitability that can lead to temporal lobe epilepsy, tonic-clonic seizures and alcohol withdrawal seizures. Similarly, BKCa channel blockade can trigger seizures and status epilepticus. Paradoxically, some mutations in BKCa channel subunit can give rise to channel gain-of-function that leads to development of idiopathic epilepsy (primarily absence epilepsy). Seizures themselves also enhance BKCa channel currents associated with neuronal hyperexcitability, and blocking BKCa channels suppresses generalized tonic-clonic seizures. Thus, both loss-of-function and gain-of-function BKCa channels might serve as molecular targets for drugs to suppress certain seizure phenotypes including temporal lobe seizures and absence seizures, respectively.
authors.affiliation: Georgetown University Medical Center, Interdisciplinary Program in Neuroscience and Department of Pediatrics, Washington, DC 20057, USA. pn@georgetown.edu
authors.forename: Prosper
authors.initials: P
authors.lastname: N'Gouemo
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D016503:Drug Delivery Systems; D004827:Epilepsy / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000927:Anticonvulsants; D051036:Large-Conductance Calcium-Activated Potassium Channels; D002118:Calcium