title: The therapeutic potential of small-conductance KCa2 channels in neurodegenerative and psychiatric diseases.
abstract: BACKGROUND
  KCa2 or small-conductance Ca(2+)-activated K(+) channels (SK) are expressed in many areas of the central nervous system where they participate in the regulation of neuronal afterhyperpolarization and excitability, and also serve as negative feedback regulators on the glutamate-NMDA pathway.
  
  
  METHODS
  This review focuses on the role of KCa2 channels in learning and memory and their potential as therapeutic targets for Alzheimer's and Parkinson's disease, ataxia, schizophrenia and alcohol dependence.
  
  
  CONCLUSIONS
  There currently exists relatively solid evidence supporting the use of KCa2 activators for ataxia. Genetic KCa2 channel suppression in deep cerebellar neurons induces ataxia, while KCa2 activators like 1-EBIO, SKA-31 and NS13001 improve motor deficits in mouse models of episodic ataxia (EA) and spinal cerebellar ataxia (SCA). Use of KCa2 activators for ataxia is further supported by a report that riluzole improves ataxia in a small clinical trial. Based on accumulating literature evidence, KCa2 activators further appear attractive for the treatment of alcohol dependence and withdrawal. Regarding Alzheimer's disease, Parkinson's disease and schizophrenia, further research, including long-term studies in disease relevant animal models, will be needed to determine whether KCa2 channels constitute valid targets and whether activators or inhibitors would be needed to positively affect disease outcomes.
authors.affiliation: University of California, Davis, Department of Pharmacology , 451 Health Sciences Drive, Genome and Biomedical Sciences Facility Room 3502, Davis, CA 95616 , USA +1 530 754 6135 ; +1 530 752 7710 ; hwulff@ucdavis.edu.
authors.forename: Jenny
authors.initials: J
authors.lastname: Lam
authors.forename: Nichole
authors.initials: N
authors.lastname: Coleman
authors.forename: April Lourdes A
authors.initials: AL
authors.lastname: Garing
authors.forename: Heike
authors.initials: H
authors.lastname: Wulff
mesh_terms: D000818:Animals; D006801:Humans; D049990:Membrane Transport Modulators / Q000494:pharmacology / Q000627:therapeutic use*; D001523:Mental Disorders / Q000188:drug therapy* / Q000503:physiopathology; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000503:physiopathology; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000502:physiology*
chemical_list: D049990:Membrane Transport Modulators; D051640:Small-Conductance Calcium-Activated Potassium Channels