Paradox of Ca2+ signaling, cell death and stroke.
Since the early 1960s it has been known that restoring extracellular Ca2+ following a period of low Ca2+ concentrations paradoxically causes an increase in intracellular Ca2+ levels that can lead to cell death. The mystery of this 'Ca2+ paradox' is made more intriguing by observations that lowering concentrations of extracellular Ca2+ and/or Mg2+ paradoxically enhances the entry of Ca2+ into hippocampal neurons. Until recently, the entry of Ca2+ through NMDA receptors was accepted as the major pathway leading to the excitotoxic, delayed cell death associated with the ischemic periods of stroke. Here, we discuss how several transient receptor potential (TRP) channels are likely to contribute to both the Ca2+ paradox and the delayed death of neurons following an ischemic stroke.
MacDonald
John F
JF
Department of Physiology, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada. j.macdonald@utoronto.ca
Xiong
Zhi-Gang
ZG
Jackson
Michael F
MF
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D016923:Cell Death / Q000502:physiology*; D006801:Humans; D017346:Protein Serine-Threonine Kinases; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D015427:Reperfusion Injury / Q000473:pathology; D020521:Stroke / Q000473:pathology* / Q000503:physiopathology*; D050053:TRPM Cation Channels / Q000502:physiology
D016194:Receptors, N-Methyl-D-Aspartate; D050053:TRPM Cation Channels; D017346:Protein Serine-Threonine Kinases; C486583:TRPM7 protein, human; D002118:Calcium