Apoptotic surface delivery of K+ channels
S K Pal1, K Takimoto, E Aizenman
1Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15217, USA.
Cell Death and Differentiation
|November 8, 2005
Summary
Apoptosis in cortical neurons involves increased Kv2.1 channel activity. New Kv2.1 channels are inserted into the cell membrane during apoptosis, leading to potassium (K+) efflux and cell death.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Apoptosis, or programmed cell death, in cortical neurons is linked to potassium (K+) efflux.
- Kv2.1 channels play a critical role in mediating this K+ efflux during neuronal apoptosis.
Purpose of the Study:
- To investigate the mechanism behind the surge in Kv2.1 channel activity during apoptosis.
- To determine if de novo channel insertion into the plasma membrane contributes to apoptotic K+ current.
Main Methods:
- Utilized a cysteine-containing Kv2.1 mutant and a thiol-reactive covalent inhibitor.
- Employed biotinylation assays to assess cell surface protein levels.
- Investigated the role of SNARE proteins using botulinum neurotoxins targeting syntaxin and SNAP-25.
Main Results:
- Demonstrated that increased K+ current during apoptosis results from the insertion of new Kv2.1 channels into the plasma membrane.
- Biotinylation experiments confirmed increased Kv2.1 protein at the cell surface after apoptotic stimuli.
- Disruption of SNARE proteins (syntaxin, SNAP-25) inhibited the surface upregulation of Kv2.1 channels.
Conclusions:
- The surge in K+ current during cortical neuron apoptosis is caused by the trafficking and insertion of functional Kv2.1 channels into the plasma membrane.
- SNARE proteins are implicated in supporting the delivery of Kv2.1 channels to the cell surface during apoptosis.
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