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

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Abstract
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 neuronsin 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.