K+-dependent cerebellar granule neuron apoptosis. Role of task leak K+ channels

Rat mature cerebellar granule, unlike hippocampal neurons, die by apoptosis when cultured in a medium containing a physiological concentration of K+ but survive under high external K+ concentrations. Cell death in physiological K+ parallels the developmental expression of the TASK-1 and TASK-3 subun...

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Bibliographic Details
Published in:The Journal of biological chemistry 2003-08, Vol.278 (34), p.32068-32076
Main Authors: Lauritzen, Inger, Zanzouri, Marc, Honoré, Eric, Duprat, Fabrice, Ehrengruber, Markus U, Lazdunski, Michel, Patel, Amanda J
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Base Sequence
Cerebellum - cytology
Cerebellum - metabolism
Cytoplasmic Granules - metabolism
DNA Primers
Gene Expression Regulation, Developmental
Hydrogen-Ion Concentration
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - physiology
Potassium - metabolism
Potassium Channels - genetics
Potassium Channels - physiology
Potassium Channels, Tandem Pore Domain
Rats
Rats, Wistar
Reverse Transcriptase Polymerase Chain Reaction
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Summary:Rat mature cerebellar granule, unlike hippocampal neurons, die by apoptosis when cultured in a medium containing a physiological concentration of K+ but survive under high external K+ concentrations. Cell death in physiological K+ parallels the developmental expression of the TASK-1 and TASK-3 subunits that encode the pH-sensitive standing outward K+ current IKso. Genetic transfer of the TASK subunits in hippocampal neurons, lacking IKso, induces cell death, while their genetic inactivation protects cerebellar granule neurons. Neuronal death of cultured rat granule neurons is also prevented by conditions that specifically reduce K+ efflux through the TASK-3 channels such as extracellular acidosis and ruthenium red. TASK leak K+ channels thus play an important role in K+-dependent apoptosis of cerebellar granule neurons in culture.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M302631200