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

Abstract

INTRODUCTION:

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.

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.

• Authors: Jenny Lam, Nichole Coleman, April Lourdes A Garing, Heike Wulff
• Journal: Expert opinion on therapeutic targets (Expert Opin Ther Targets) Vol. 17 Issue 10 Pg. 1203-20 (Oct 2013) ISSN: 1744-7631 [Electronic] England
• PMID: 23883298 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)

Chemical References

• Membrane Transport Modulators
• Small-Conductance Calcium-Activated Potassium Channels

Topics

• Animals
• Humans
• Membrane Transport Modulators (pharmacology, therapeutic use)
• Mental Disorders (drug therapy, physiopathology)
• Neurodegenerative Diseases (drug therapy, physiopathology)
• Small-Conductance Calcium-Activated Potassium Channels (physiology)