“…Injurious stimuli promote the N-terminal proteolytic cleavage of BCL-xL to form the killer protein ⌬N-BCL-xL (Cheng et al, 1997), which induces large conductance channels in mitochondrial outer membranes (Jonas et al, 2004 and cytochrome c release (Clem et al, 1998;Fujita et al, 1998). Zn 2ϩ is normally abundant in hippocampus (Frederickson et al, 1982;Assaf and Chung, 1984;Frederickson and Danscher, 1990;Tonder et al, 1990;Danscher et al, 1997;Li et al, 2001) (but see Kay, 2003) and at high concentrations is a mediator of neuronal death (Koh et al, 1996;Choi and Koh, 1998;Weiss and Sensi, 2000;Bossy-Wetzel et al, 2004;Sensi and Jeng, 2004;Zukin et al, 2004). Global ischemia elicits a delayed rise in Zn 2ϩ in CA1 neurons before death (Koh et al, 1996;Choi and Koh, 1998;Calderone et al, 2004); evidence suggests that Zn 2ϩ enters through GluR2 (glutamate receptor subunit 2)-lacking AMPA receptors (Sensi et al, 1999;Yin et al, 2002) and is released from intracellular stores (Aizenman et al, 2000;Lee et al, 2000;Sensi et al, 2003a;Bossy-Wetzel et al, 2004).…”