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Sodium Calcium Exchange: A Growing Spectrum of Pathophysiological Implications

Volume 961 of the series Advances in Experimental Medicine and Biology pp 433-447

Date:

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

  • John F. MacDonaldAffiliated withDepartment of Anatomy and Cell Biology, University of Western OntarioRobarts Research Institute, Molecular Brain Research Group, University of Western OntarioDepartment of Physiology and Pharmacology, University of Western Ontario Email author 
  • , Jillian C. BelroseAffiliated withDepartment of Anatomy and Cell Biology, University of Western OntarioRobarts Research Institute, Molecular Brain Research Group, University of Western Ontario
  • , Yu-Feng XieAffiliated withRobarts Research Institute, Molecular Brain Research Group, University of Western Ontario
  • , Michael F. JacksonAffiliated withRobarts Research Institute, Molecular Brain Research Group, University of Western OntarioDepartment of Physiology and Pharmacology, University of Western Ontario

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Abstract

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.

Keywords

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