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Monitoring Dynamic Changes In Mitochondrial Calcium Levels During Apoptosis Using A Genetically Encoded Calcium Sensor
06:26

Monitoring Dynamic Changes In Mitochondrial Calcium Levels During Apoptosis Using A Genetically Encoded Calcium Sensor

Published on: April 1, 2011

Window current through the T-type Ca2+ channel triggers the mechanism for cellular apoptosis via mitochondrial

Tomoko Uchino1, Shojiro Isomoto, Takayuki Noguchi

  • 1Department of Pathophysiology, Oita University School of Medicine, 1-1 Idaigaoka, Hasama, Yufu, Oita, 879-5593, Japan.

Heart and Vessels
|January 19, 2013
PubMed

Insights

Calcium (Ca2+) entry via T-type calcium channels triggers apoptosis through mitochondrial pathways. Blocking these channels with efonidipine prevents this cell death, suggesting new therapeutic targets.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Physiology

Background:

  • Apoptosis, or programmed cell death, is crucial for development and tissue homeostasis.
  • Dysregulation of apoptosis is implicated in various diseases, including cancer and neurodegenerative disorders.
  • T-type calcium channels (TTCCs) play roles in various cellular functions, but their direct role in apoptosis is not fully understood.

Purpose of the Study:

  • To investigate the hypothesis that Ca(2+) influx through TTCCs induces apoptosis.
  • To elucidate the specific role of Cav3.2 TTCCs in high extracellular Ca(2+)]-induced apoptosis.
  • To explore the potential of TTCCs as therapeutic targets for diseases involving abnormal apoptosis.

Main Methods:

  • Transfection of human embryonic kidney (HEK) 293 cells with Cav3.2 TTCCs (HEK-Cav3.2 cells).
  • Exposure of HEK-Cav3.2 cells and control HEK293 cells to high extracellular Ca(2+) media (7.2 mM).
  • Assessment of apoptosis using hypodiploid DNA content, mitochondrial membrane potential, and caspase activation (caspase-3, -9, and -8).
  • Pharmacological inhibition of TTCCs using the selective blocker R(-)-efonidipine.

Main Results:

  • High extracellular Ca(2+) increased intracellular Ca(2+) in HEK-Cav3.2 cells but not in control cells.
  • Apoptosis, characterized by hypodiploidy, mitochondrial dysfunction, and caspase-3/-9 activation, was observed in HEK-Cav3.2 cells under high Ca(2+) conditions.
  • R(-)-efonidipine treatment significantly blunted the high Ca(2+)]-induced apoptotic changes.
  • No apoptosis was induced in untransfected HEK293 cells under identical conditions.

Conclusions:

  • Ca(2+) entry through the steady-state window current of TTCCs directly causes apoptosis via mitochondrial pathways.
  • TTCCs represent potential novel therapeutic targets for diseases associated with aberrant apoptosis.
  • Targeting TTCCs may offer a new strategy for managing conditions characterized by excessive or insufficient cell death.

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