Dataset Information

Convergent Ca2+ and Zn2+ signaling regulates apoptotic Kv2.1 K+ currents.

ABSTRACT: A simultaneous increase in cytosolic Zn(2+) and Ca(2+) accompanies the initiation of neuronal cell death signaling cascades. However, the molecular convergence points of cellular processes activated by these cations are poorly understood. Here, we show that Ca(2+)-dependent activation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is required for a cell death-enabling process previously shown to also depend on Zn(2+). We have reported that oxidant-induced intraneuronal Zn(2+) liberation triggers a syntaxin-dependent incorporation of Kv2.1 voltage-gated potassium channels into the plasma membrane. This channel insertion can be detected as a marked enhancement of delayed rectifier K(+) currents in voltage clamp measurements observed at least 3 h following a short exposure to an apoptogenic stimulus. This current increase is the process responsible for the cytoplasmic loss of K(+) that enables protease and nuclease activation during apoptosis. In the present study, we demonstrate that an oxidative stimulus also promotes intracellular Ca(2+) release and activation of CaMKII, which, in turn, modulates the ability of syntaxin to interact with Kv2.1. Pharmacological or molecular inhibition of CaMKII prevents the K(+) current enhancement observed following oxidative injury and, importantly, significantly increases neuronal viability. These findings reveal a previously unrecognized cooperative convergence of Ca(2+)- and Zn(2+)-mediated injurious signaling pathways, providing a potentially unique target for therapeutic intervention in neurodegenerative conditions associated with oxidative stress.

SUBMITTER: McCord MC

PROVIDER: S-EPMC3752224 | biostudies-other | 2013 Aug

REPOSITORIES: biostudies-other

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Convergent Ca2+ and Zn2+ signaling regulates apoptotic Kv2.1 K+ currents.

McCord Meghan C MC Aizenman Elias E

Proceedings of the National Academy of Sciences of the United States of America 20130805 34

A simultaneous increase in cytosolic Zn(2+) and Ca(2+) accompanies the initiation of neuronal cell death signaling cascades. However, the molecular convergence points of cellular processes activated by these cations are poorly understood. Here, we show that Ca(2+)-dependent activation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is required for a cell death-enabling process previously shown to also depend on Zn(2+). We have reported that oxidant-induced intraneuronal Zn(2+) liberati ...[more]

PMID: 23918396

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Dataset Information

Convergent Ca2+ and Zn2+ signaling regulates apoptotic Kv2.1 K+ currents.

Publications

Convergent Ca2+ and Zn2+ signaling regulates apoptotic Kv2.1 K+ currents.

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