436
Views
37
CrossRef citations to date
0
Altmetric
Reviews

The therapeutic potential of small-conductance KCa2 channels in neurodegenerative and psychiatric diseases

, MD, , , MD & , PhD
Pages 1203-1220 | Published online: 25 Jul 2013
 

Abstract

Introduction: KCa2 or small-conductance Ca2+-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.

Areas covered: 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.

Expert opinion: 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.

Notes

This box summarizes key points contained in the article.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.