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Published on: May 10, 2017
Role for ionic fluxes on cell death and apoptotic volume decrease in cultured cerebellar granule neurons
B Hernández-Enríquez1, R O Arellano, J Morán
1Division of Neurosciences, Institute of Cell Physiology, National Autonomous University of Mexico, Circuito Exterior S/N, Ciudad Universitaria, 04510 Mexico City, Mexico.
Neuroscience
|February 11, 2010
Summary
Ionic fluxes are crucial for cerebellar granule neuron apoptosis. Potassium and chloride channel blockers differentially affect apoptotic volume decrease and cell death, depending on the apoptotic trigger.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Apoptotic cell death involves significant ionic flux changes.
- Cerebellar granule neurons (CGN) are a model for studying apoptosis.
- Ionic fluxes, particularly potassium and chloride, are implicated in apoptotic volume decrease (AVD).
Purpose of the Study:
- To investigate the role of specific ion channel blockers in CGN apoptosis.
- To determine if potassium and chloride channel blockers differentially affect AVD and cell death.
- To elucidate the mechanisms of ionic flux involvement in CGN apoptosis induced by different stimuli.
Main Methods:
- CGN were induced to undergo apoptosis using staurosporine, camptothecin (CPT), or high-to-low extracellular potassium shift (K25 to K5).
- Apoptotic volume decrease, caspase-3 activation, nuclear condensation, and cell death were measured.
- Potassium channel blockers (cesium [Cs+], tetraethylammonium [TEA+]) and chloride channel blockers (DIDS) were applied.
- Membrane currents were measured under K5 conditions.
Main Results:
- All three apoptotic conditions induced AVD in CGN.
- Cs+ and TEA+ blocked AVD, caspase-3 activation, nuclear condensation, and cell death induced by K5 and CPT, but not staurosporine.
- Cs+ and TEA+ blocked membrane currents in K5 conditions.
- DIDS blocked cell volume loss induced by K5 or staurosporine.
- Only DIDS protected CGN from staurosporine-induced death.
Conclusions:
- Ionic fluxes are critical for AVD and apoptotic death in CGN.
- The specific ion channels involved in AVD and cell death depend on the apoptotic stimulus.
- Potassium channels are key in K5 and CPT-induced apoptosis, while chloride channels are involved in staurosporine-induced AVD and death.
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