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Updated: Jul 15, 2026

Demonstration of Proteolytic Activation of the Epithelial Sodium Channel (ENaC) by Combining Current Measurements with Detection of Cleavage Fragments
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Demonstration of Proteolytic Activation of the Epithelial Sodium Channel (ENaC) by Combining Current Measurements with Detection of Cleavage Fragments

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The plasma membrane Na+/Ca2+ exchanger is cleaved by distinct protease families in neuronal cell death

D Bano1, E Munarriz, H L Chen

  • 1MRC Toxicology Unit, University of Leicester, Hodgkin Building, Lancaster Road LE1 9HN, Leicester, UK. db81@le.ac.uk

Annals of the New York Academy of Sciences
|April 21, 2007
PubMed

Insights

Calcium (Ca2+) deregulation is implicated in neurodegenerative cell death. This study reveals that the sodium-calcium exchanger (NCX) is cleaved by caspases during apoptosis, highlighting its lethal role in neuronal death.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Neurodegenerative diseases involve neuronal dysfunction and cell death.
  • Calcium (Ca2+) deregulation is a common factor in neuronal cell death pathways.
  • The plasma membrane sodium-calcium exchanger (NCX) regulates intracellular Ca2+ levels.

Purpose of the Study:

  • To investigate the role of the NCX in neuronal apoptosis.
  • To determine if NCX is modulated by caspases, key mediators of apoptosis.
  • To understand the impact of NCX cleavage on neuronal cell death.

Main Methods:

  • Neuronal cell culture models.
  • Induction of apoptosis and necrosis.
  • Western blotting and mass spectrometry to detect protein cleavage.
  • Calcium imaging techniques.

Main Results:

  • Neurons undergoing apoptosis exhibit caspase-mediated cleavage of the NCX.
  • This cleavage disrupts the primary Ca2+ extrusion pathway in neurons.
  • Similar to calpain-mediated cleavage in necrosis, caspase-mediated NCX cleavage contributes to cell death.

Conclusions:

  • Cleavage of the NCX by caspases is a critical event in neuronal apoptosis.
  • Targeting NCX cleavage may offer therapeutic strategies for neurodegenerative conditions.
  • Modulation of the NCX is a common lethal mechanism across different cell death pathways.

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