Nonselective Cation Channels and Links to Hippocampal Ischemia, Aging, and Dementia

  • John F. MacDonaldEmail author
  • Jillian C. Belrose
  • Yu-Feng Xie
  • Michael F. Jackson
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 961)


Stroke is a very strong risk factor for dementia. Furthermore, ischemic stroke and Alzheimer’s disease (AD) share a number of overlapping mechanisms of neuron loss and dysfunction, including those induced by the inappropriate activation of N-methyl-d-aspartate receptors (NMDARs). These receptors form a major subtype of excitatory glutamate receptor. They are nonselective cation channels with appreciable Ca2+ permeability, and their overactivation leads to neurotoxicity in the cortex and hippocampus. NMDARs have therefore been therapeutic targets in both conditions, but they have failed in the treatment of stroke, and there is limited rationale for using them in treating AD. In this chapter, we discuss current understanding of subtypes of NMDARs and their potential roles in ­ischemic stroke and AD. We also discuss the properties of several other nonselective cation channels, transient receptor potential melastatin 2 and 7 channels, and their implications in linking these conditions.


N-methyl-d-aspartate receptors (NMDA receptors) Transient receptor potential melastatin channels (TRPM7, TRPM2) Src family kinases Stroke Alzheimer’s disease 


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • John F. MacDonald
    • 1
    • 2
    • 3
    Email author
  • Jillian C. Belrose
    • 1
    • 2
  • Yu-Feng Xie
    • 2
  • Michael F. Jackson
    • 2
    • 3
  1. 1.Department of Anatomy and Cell BiologyUniversity of Western OntarioLondonCanada
  2. 2.Robarts Research Institute, Molecular Brain Research GroupUniversity of Western OntarioLondonCanada
  3. 3.Department of Physiology and PharmacologyUniversity of Western OntarioLondonCanada

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