The release of glutamate during brain anoxia or ischaemia triggers the death of neurons, causing mental or physical handicap. The mechanism of glutamate release is controversial, however. Four release mechanisms have been postulated: vesicular release dependent on external calcium or Ca2+ released from intracellular stores; release through swelling-activated anion channels; an indomethacin-sensitive process in astrocytes; and reversed operation of glutamate transporters. Here we have mimicked severe ischaemia in hippocampal slices and monitored glutamate release as a receptor-gated current in the CA1 pyramidal cells that are killed preferentially in ischaemic hippocampus. Using blockers of the different release mechanisms, we demonstrate that glutamate release is largely by reversed operation of neuronal glutamate transporters, and that it plays a key role in generating the anoxic depolarization that abolishes information processing in the central nervous system a few minutes after the start of ischaemia. A mathematical model incorporating K+ channels, reversible uptake carriers and NMDA (N-methyl-D-aspartate) receptor channels reproduces the main features of the response to ischaemia. Thus, transporter-mediated glutamate homeostasis fails dramatically in ischaemia: instead of removing extracellular glutamate to protect neurons, transporters release glutamate, triggering neuronal death.

We find upper and lower bounds of the multiplicities of irreducible admissible representations $\pi$ of a semisimple Lie group $G$ occurring in the induced representations $Ind_H^G\tau$ from irreducible representations $\tau$ of a closed subgroup $H$. As corollaries, we establish geometric criteria for finiteness of the dimension of $Hom_G(\pi,Ind_H^G \tau)$ (induction) and of $Hom_H(\pi|_H,\tau)$ (restriction) by means of the real flag variety $G/P$, and discover that uniform boundedness property of these multiplicities is independent of real forms and characterized by means of the complex flag variety.Comment: to appear in Advances in Mathematic

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