Mediation of neuronal apoptosis by Kv2.1-encoded potassium channels.
Cellular K+ efflux is a requisite event in the unfolding of apoptosis programs across many types of cells and death-inducing stimuli; however, the molecular identities of the ion channels mediating this key event have remained undefined. Here, we show that Kv2.1-encoded K+ channels are responsible for the expression of apoptosis in cortical neurons in vitro. Transient expression of two different dominant-negative forms of this subunit in neurons completely eliminated the enhancement of K+ currents that normally accompanies the cell death process. Importantly, neurons deficient in functional Kv2.1-encoded K+ channels were protected from oxidant and staurosporine-induced apoptosis. Finally, Chinese hamster ovary cells, which do not express endogenous voltage-gated K+ channels, became substantially more sensitive to apoptosis after transient expression of wild-type Kv2.1. These results suggest that Kv2.1-encoded K+ channels are necessary for the apoptotic signaling cascade in mammalian cortical neurons in culture and are sufficient for increasing the susceptibility to apoptogens in a nonexcitable cell.
Pal
Sumon
S
Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
Hartnett
Karen A
KA
Nerbonne
Jeanne M
JM
Levitan
Edwin S
ES
Aizenman
Elias
E
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D019610:Cytoprotection / Q000235:genetics / Q000502:physiology; D051668:Delayed Rectifier Potassium Channels; D005799:Genes, Dominant; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D016877:Oxidants / Q000633:toxicity; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D051381:Rats; D051669:Shab Potassium Channels; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D019311:Staurosporine / Q000633:toxicity; D014162:Transfection
D051668:Delayed Rectifier Potassium Channels; C496991:Kcnb1 protein, rat; D016877:Oxidants; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D021122:Protein Subunits; D051669:Shab Potassium Channels; D019311:Staurosporine; D011188:Potassium