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

Jenny Lam, Nichole Coleman, April Lourdes A Garing, Heike Wulff

Research output: Contribution to journalArticle

26 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1203-1220
Number of pages18
JournalExpert Opinion on Therapeutic Targets
Volume17
Issue number10
DOIs
StatePublished - Oct 2013

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Ataxia
Neurodegenerative Diseases
Psychiatry
Alcoholism
Parkinson Disease
Schizophrenia
Alzheimer Disease
Riluzole
Alcohols
Therapeutics
Animal Disease Models
Calcium-Activated Potassium Channels
Cerebellar Ataxia
Expert Testimony
Neurology
N-Methylaspartate
Neurons
Glutamic Acid
Animals
Central Nervous System

Keywords

  • 1-EBIO
  • Afterhyperpolarization
  • Alcohol dependence and withdrawal
  • Alzheimer's disease
  • Apamin
  • Ataxia
  • Calcium-activated potassium channel
  • KCa2
  • Learning and memory
  • NS13001
  • NS309
  • Parkinson's disease
  • Riluzole
  • Schizophrenia
  • SKA-31
  • Small-conductance

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Clinical Biochemistry
  • Molecular Medicine

Cite this

The therapeutic potential of small-conductance KCa2 channels in neurodegenerative and psychiatric diseases. / Lam, Jenny; Coleman, Nichole; Garing, April Lourdes A; Wulff, Heike.

In: Expert Opinion on Therapeutic Targets, Vol. 17, No. 10, 10.2013, p. 1203-1220.

Research output: Contribution to journalArticle

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