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Controlling Bad Calcium

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Science  23 Jul 2004:
Vol. 305, Issue 5683, pp. 453
DOI: 10.1126/science.305.5683.453c

Transient ischemia, as occurs during stroke, kills some neurons—particularly CA1 pyramidal neurons of the hippocampus—but not others. Susceptibility is associated with the influx of Ca2+ or Zn2+ through AMPA (α-amino-3-hydroxyl-5-methyl-4-isoxazoleproprionic acid) receptor channels, which are activated by the neurotransmitter glutamate. Not all AMPA receptors conduct Ca2+, and the identity of an amino acid [arginine (R) or glutamine (Q)] in the GluR2 subunit is the critical determinant. Liu et al. expressed the GluR2(R) subunit in the rat hippocampus, and this blocked the inward flux of Ca2+ and protected the CA1 pyramidal cells from ischemia-induced injury. Conversely, expressing the Ca2+-permeable GluR2(Q) subunits in neurons in the CA3 area and dentate gyrus of the hippocampus, which normally are not susceptible, resulted in cell death after an ischemic insult. Therapeutic strategies aimed at protecting neurons with AMPA antagonists are problematic because glutamate receptors on uninjured cells are also blocked, but selective inhibition of the Ca2+ permeability of AMPA receptors may offer another path to treatment. — LBR

Neuron 43, 43 (2004).

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