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Related Experiment Videos

Receptor-mediated control of regulatory volume decrease (RVD) and apoptotic volume decrease (AVD).

Y Okada1, E Maeno, T Shimizu

  • 1Department of Cell Physiology, National Institute for Physiological Sciences, Okazaki 444-8585, Japan. okada@nips.ac.jp

The Journal of Physiology
|April 3, 2001
PubMed
Summary
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Animal cells regulate volume via regulatory volume decrease (RVD) involving KCl efflux. This study reveals how purinergic and Ca2+-sensing receptors modulate RVD and apoptotic volume decrease (AVD) through shared signaling pathways.

Area of Science:

  • Cell Biology
  • Physiology
  • Molecular Biology

Background:

  • Animal cells possess a fundamental ability to regulate their volume, particularly under osmotic stress.
  • Regulatory volume decrease (RVD) is a key mechanism involving KCl efflux through activated K+ and Cl- channels.
  • Apoptotic volume decrease (AVD) is linked to cell death initiation and involves normotonic cell shrinkage.

Purpose of the Study:

  • To investigate the molecular mechanisms of RVD in human epithelial cells (Intestine 407).
  • To explore the roles of purinergic ATP (P2Y2) receptors and Ca2+-sensing receptors (CaR) in RVD.
  • To elucidate the relationship between AVD, RVD, and shared signaling pathways in cell volume regulation and survival.

Main Methods:

  • Studied RVD in Intestine 407 cells under osmotic stress.

Related Experiment Videos

  • Investigated the impact of ATP release and purinergic receptor stimulation on RVD.
  • Examined the role of CaR in modulating volume-sensitive Cl- channels.
  • Analyzed AVD induction by death receptors in various cell lines (U937, HeLa, NG108-15, PC12).
  • Utilized blockers of volume-regulatory K+ and Cl- channels to assess AVD mechanisms.
  • Main Results:

    • Osmotic swelling increased cytosolic Ca2+, activating IK channels and inducing ATP release.
    • Released ATP stimulated P2Y2 receptors, enhancing RVD via Ca2+ mobilization and IK channel augmentation.
    • CaR stimulation augmented volume-sensitive outwardly rectifying Cl- channels, facilitating RVD.
    • AVD induction by death receptors was observed in multiple cell types and facilitated RVD.
    • Blockade of volume-regulatory ion channels inhibited AVD and subsequent apoptotic events.

    Conclusions:

    • RVD is facilitated by P2Y2 receptor stimulation and CaR activation, involving Ca2+ mobilization and augmentation of specific ion channels.
    • AVD shares common downstream signaling pathways with RVD, suggesting a link between volume regulation and cell death.
    • Understanding these receptor-mediated processes provides insights into cell volume control and survival mechanisms.