RT Journal Article
SR Electronic
T1 Mediation of Neuronal Apoptosis by Kv2.1-Encoded Potassium Channels
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 4798
OP 4802
DO 10.1523/JNEUROSCI.23-12-04798.2003
VO 23
IS 12
A1 Sumon Pal
A1 Karen A. Hartnett
A1 Jeanne M. Nerbonne
A1 Edwin S. Levitan
A1 Elias Aizenman
YR 2003
UL http://www.jneurosci.org/content/23/12/4798.abstract
AB 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.