Semenova et al. claim that a "necessary and sufficient" death program was activated by just a few seconds in 30 mM KCl. But when the trail of references is traced backwards to find their culture conditions, it seems that the cerebellar granule cells they used were routinely cultured in 25 mM KCl. Can a 5 mM elevation of KCl for just a few seconds really kill cerebellar granule cells? These authors and others have shown previously that high KCl is necessary for cerebellar granule cell survival. Other reports indicate that glutamate itself is a survival factor for these cells.

It would also have been nice to see citation of Bossy-Wetzel et al. (2004). These authors showed evidence for a different mechanism to activate p38 by NMDA receptors—one that could explain a caspase-independent programmed cell death that is sensitive to Bcl-2.

References:
Bossy-Wetzel E, Talantova MV, Lee WD, Scholzke MN, Harrop A, Mathews E, Gotz T, Han J, Ellisman MH, Perkins GA, Lipton SA. Crosstalk between nitric oxide and zinc pathways to neuronal cell death involving mitochondrial dysfunction and p38-activated K+ channels. Neuron. 2004;41:351-65. Abstract

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