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The Journal of Neuroscience, June 15, 2003, 23(12):4798-4802

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BRIEF COMMUNICATION
Mediation of Neuronal Apoptosis by Kv2.1-Encoded Potassium Channels

Sumon Pal,¹ Karen A. Hartnett,¹ Jeanne M. Nerbonne,³ Edwin S. Levitan,² and Elias Aizenman¹

Departments of ¹Neurobiology, ²Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, and ³Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110

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.

Key words: potassium channels; Kv2.1; apoptosis; neurotoxicity; cortical neurons; Chinese hamster ovary; luciferase; transfection

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Received Jan. 27, 2003; revised Apr. 9, 2003; accepted Apr. 9, 2003.

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